| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1995;92:1479-1486.)
© 1995 American Heart Association, Inc.
Articles |
Tumor Necrosis Factor Soluble Receptors in Patients With Various Degrees of Congestive Heart Failure
From the Cattedra di Cardiologia, Università degli Studi di Brescia (R.F., R.C., O.V.); the Centro di Fisiopatologia Cardiovascolare "Salvatore Maugeri," Fondazione Clinica del Lavoro, Gussago, Brescia (T.B.); the Heart Failure Unit, Fondazione Clinica del Lavoro, Montescano, Pavia (C.O., O.F.); and Tecnogen ScpA, Piana di Monte Verna, Caserta (A.C., G.C.), Italy.
Correspondence to Prof Roberto Ferrari, Cattedra di Cardiologia, Università degli Studi di Brescia, c/o Spedali Civili, P.le Spedali Civili, 1, 25123 Brescia, Italy.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Background Tumor necrosis factor alpha (TNF-
)
increases in patients with severe congestive heart failure (CHF) and
cachexia. Two naturally occurring modulators of TNF- activity have
been identified in human serum. These two soluble proteins are the
extracellular domains of the TNF receptors (sTNF-RI and sTNF-RII,
respectively). The determination of circulating sTNF-Rs could provide
us with some additional information about the activation of this
cytokine in CHF.
Methods and Results This study was undertaken to examine the
concentration of sTNF-Rs and of bioactive and antigenic TNF- in 37
consecutive patients with various degrees of CHF compared with that of
26 age-matched healthy subjects. Antigenic TNF- increased (from
14.3±7.08 to 33.5±13.1 pg/mL, P<.001) in preterminal
patients with severe CHF (New York Heart Association [NYHA] class
IV). In these patients, sTNF-Rs were also increased (sTNF-RI from
1.17±0.43 to 4.43±2.14 ng/mL and sTNF-RII from 2.2±0.44
to
7.55±2.28 ng/mL, P<.001). When measured by cytolytic
bioassay, TNF- was undetectable (<100 pg/mL). Addition of 625 pg/mL
recombinant human TNF- (rhTNF-), corresponding in the bioassay to
60% of the lethal dose, to the serum of healthy subjects resulted in a
significant increase of the expected cytotoxicity (from 625 to
1290±411 pg/mL, P<.001). Addition of the same dose of
rhTNF- to the serum of patients with mild to moderate CHF (NYHA
classes II and III) increased the cytotoxicity from 625 to 877±132
pg/mL, P<.001. In 4 patients with severe CHF (class IV),
the expected cytotoxicity was completely inhibited, whereas it was
reduced from 625 to 263±198 pg/mL, P<.001, in the
remaining 8 patients. Ten patients died within 1 month of entry into
the study. They had the highest level of sTNF-RII (8.18±1.92 ng/mL).
sTNF-RII was a more powerful independent indicator of mortality than
TNF-, sTNF-RI, NYHA class, norepinephrine, and atrial
natriuretic peptide.
Conclusions Measurement of sTNF-Rs, in addition to antigenic and
bioactive TNF-, is essential for evaluation of the activation of
this cytokine in CHF. Both sTNF-Rs increase in preterminal
patients with severe CHF and might inhibit the in vitro cytotoxicity of
TNF-. Antigenic TNF- also increases in severe CHF. The increased
levels of sTNF-RII independently correlate with poor short-term
prognosis.
Key Words: hormones • proteins • heart failure • receptors
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Recent studies report that tumor necrosis factor alpha (TNF-
) is increased in patients with severe congestive
heart failure
(CHF).1 2 3 4 5
Earlier studies showed that
TNF- elevation was associated with cachexia1 2
and with
a marked activation of the renin-angiotensin system.1
However, a prospective study undertaken to assess serial changes in
TNF- during a period of 1 year showed no correlation between
TNF-, plasma norepinephrine, renin activity, and patient
weight.3 In these studies, measurements of TNF- were
carried out either by ELISA or radioimmunoassay
methods2 3
to detect antigenic TNF- or by a cytotoxicity bioassay that
detects only biologically active (cytolytic)
TNF-.1 6 7
Irrespective of the methodology used, there was a wide variation in
plasma values of TNF- between and within patients. In several
patients, circulating TNF- was not detected despite the presence
of severe CHF.
Two TNF receptors of 55 and 75 kD, TNF-RI and TNF-RII, have been
identified on the surface of several cell lines and are thought to
mediate and regulate most of the effects of TNF.8 9
The
extracellular domain fragments of both receptors shed from cell
surfaces can be detected as soluble forms (sTNF-RI and sTNF-RII) in the
urine and blood. These soluble proteins are supposed to regulate the
TNF- bioactivity either by inhibiting the binding of TNF trimers to
the membrane receptors10 or by preventing TNF- trimers
from dissociation to inactive monomers.11 12
Therefore,
measurements of circulating levels of sTNF-Rs provide more complete
information on TNF- activation in CHF.
The objective of this study was to further investigate the activation
of this cytokine in CHF. To this end, we determined bioactive TNF-,
antigenic TNF-, and both the sTNF-Rs in 37 consecutive patients with
various degrees of heart failure and then compared these data with
those of 26 age-matched healthy subjects.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Patient Population
This study was carried out at the Cardiology Department of the University of Brescia and at the Heart Failure Unit of the Fondazione Clinica del Lavoro, Montescano, Pavia, Italy.
Thirty-seven consecutive patients admitted for investigation or
treatment of CHF gave informed consent and were studied in compliance
with ethical approval. Table 1
shows the
characteristics of these patients. The average age was 50±10 years.
Twenty-six were men and 11, women. The cause of heart failure was
coronary artery disease in 19 patients, idiopathic dilated
cardiomyopathy in 14, and valvular diseases
in 4. Fourteen were in New York Heart Association (NYHA) clinical class
II; their mean left ventricular ejection fraction,
calculated from the two-dimensional echocardiogram, was 26±6%, and
their peak oxygen consumption was 16±5
mL · kg-1 · min-1. Eleven
patients
were in NYHA class III, with an ejection fraction of 22±8% and peak
oxygen consumption of 10±4
mL · kg-1 · min-1. Twelve
patients
were in NYHA class IV. Their mean ejection fraction was 18±5%.
|
Hemodynamics were measured in the postabsorptive state with a Swan-Ganz catheter. Cardiac output was determined by thermodilution with a Gould model SP 1445 cardiac output computer.
All patients were treated with angiotensin-converting enzyme inhibitors and, when necessary, with digoxin, diuretics, and positive inotropic agents.
No patient had received anti-inflammatory drugs within the preceding 2 weeks. At the beginning of the study, treatment was optimized and kept constant when possible.
Patients with significant concomitant disease such as infection, renal failure, pulmonary disease, thyroid disease, malignancy, or collagen vascular disease were not studied.
The control subjects consisted of 26 healthy volunteers, 18 men and 8 women, 30 to 62 years of age (mean, 48±8 years). None of them were admitted to the hospital, had acute or chronic illness, or reported any symptoms related to the cardiovascular system.
After 30 minutes of
supine rest, venous blood was taken and
centrifuged within 1 hour for measurement of serum
electrolytes, norepinephrine, epinephrine,
aldosterone, plasma renin activity, atrial
natriuretic peptide (ANP), TNF-, and sTNF-RI and
sTNF-RII. All blood samples were stored at -80°C until the
assay.
In 2 critical patients, the TNF system was monitored over time, during the last 4 and 5 days of life, respectively.
Plasma Hormones
The techniques used have been described in
detail
elsewhere.13 14 15 Plasma norepinephrine
and
epinephrine levels were measured by high-performance
liquid chromatography with electrochemical detection.
Levels of plasma renin activity, aldosterone, and ANP were
measured by radioimmunoassay. The radioimmunoassay for ANP was preceded
by a solid-phase extraction (Sep-Pak C-18 Cartridges,
Waters/Millipore). Synthetic h-ANP and rabbit anti–h-ANP
antibody (Elken Immunochemical) were used as previously
described.16
TNF- Immunoactivity
Antigenic TNF- was determined
according to the
manufacturer's instructions (Technogenetics) by a sandwich ELISA with
a commercially available kit. The mixture of monoclonal antibodies used
does not neutralize TNF- bioactivity, allowing measurement of the
total circulating TNF-. The sensitivity of the assay is 3 pg/mL.
Intra-assay and interassay coefficients of variation (CVs) are <5.2%
and <9.9%, respectively.
TNF- Cytotoxicity
Cytotoxicity was assessed by means of
an L-M fibroblast bioassay
as described by Nargi and Yang17 and slightly modified by
us. Mouse L-M fibroblasts (ATCC CCL 1.2) were grown in 96-well plates
(Falcon, Becton-Dickinson) in minimum essential medium with Earle's
salts (Gibco), supplemented with 5% FCS and 2 mmol/L glutamine at
37°C in a humidified atmosphere of 5% CO2/95%
air. One hundred microliters of a suspension of cells (300 000/mL
culture medium) was plated in each well and allowed to grow for 24
hours. Twenty-five microliters of serum sample diluted with 25 µL of
culture medium was added to each well and incubated overnight in the
presence of 50 µL of a solution containing 8 µg/mL actinomycin D
(Sigma). Thus, the final dilution of the serum in each well was 1:8.
Live cells were then stained with 5 mg/mL thiazolyl blue (MTT,
Calbiochem) for 4 hours. After aspiration of the supernatant, 200 µL
of dimethyl sulfoxide was added to each well, and the optical density
was read by a microplate reader (Biorad) at 595 nm. Bioactive TNF-
in serum samples was calculated by interpolation of the absorbance
values on a calibration curve obtained with rhTNF- standard
solutions (Tecnogen). The distribution of the curve is not linear, and
semilogarithmic plotting yields a sigmoidal curve. One hundred percent
of the lethal dose occurs at 2000 pg/mL. The sensitivity of the assay
is 100 pg/mL. Intra-assay and interassay CVs are <15% and <30%.
To
confirm whether the cytotoxicity observed was specifically due to
TNF-, the bioassay was repeated with a rabbit polyclonal
neutralizing antibody (0.2 µL/well) against rhTNF- (Genzyme).
The presence of sTNF-Rs in the serum may modulate TNF- biological
activity. To investigate this possibility, in a separate series of
experiments, we added rhTNF- at a final concentration of 625 pg/mL
(corresponding in the bioassay to 60% of the lethal dose) to each
sample lacking nonspecific cytotoxicity. The cytotoxicity of these
spiked samples was then reassessed.
sTNF-RI Assay
Serum sTNF-RI levels were assessed with a
sandwich ELISA. Two
monoclonal antibodies against human sTNF-RI, 7H3 and 9B11, that had
been generated by our group were used as previously
described.18 Microtiter plates were coated with 7H3 by
overnight incubation at 4°C with a 7H3 solution, 10 µg/mL in PBS,
100 µL/well. All subsequent steps were carried out at room
temperature. After a rinse with PBS, the uncoated plastic surface was
blocked by a 2-hour incubation with 200 µL/well of blocking buffer
(0.5% BSA, 0.05% Tween 20 in PBS) and then rinsed again. Serum
samples were mixed 2:1 with biotin-9B11 (1:2000 in blocking buffer) and
preincubated for 1 hour. Then, 150 µL of each mixture was added to
different wells and further incubated for 2 hours under gentle mixing
by a plate vortex. After thorough washing, the plates were further
incubated with 100 µL/well of a streptavidin-peroxidase solution,
1:1000 in blocking buffer (Janssen Biochimica). After a final wash,
each well was incubated for 1 hour with 200 µL of a 10 mg/mL ABTS
chromogenic solution (Boehringer Mannheim Italia),
and the absorbances at 405 nm were measured. The sensitivity of the
assay is 0.3 ng/mL. Intra-assay and interassay CVs were <6.4% and
<10%, respectively.
sTNF-RII Assay
Serum sTNF-RII levels were assessed according
to the
manufacturer's specifications by an ELISA kit (Quantikine) available
from Research and Diagnostics Systems. The minimum
detectable dose is 5 pg/mL. Intra-assay and interassay CVs were <5.1%
and <10%, respectively.
Statistical Analysis
Values are expressed as mean±SD.
The results were considered to
be significant if P<.05. The statistical significance was
estimated among the various groups by one-way ANOVA. Group-to-group
comparison was done with Student's t test. Correlations
between TNF-, sTNF-Rs, and the other parameters were
tested by Pearson analysis. Independent prognostic values of
each parameter were assessed by stepwise discriminant
analysis (BMDP PC-90 "7M").
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Table 1
shows the clinical and plasma hormone data of
patients. The average cardiac index was 0.8, 0.7, and 0.6 times lower
than normal in NYHA classes II, III, and IV, respectively. In class IV
patients, right atrial and pulmonary pressures were high (13±3
and 46±13 mm Hg) and serum levels of sodium were low (131±7
mmol/L). In class II patients, the plasma concentration of norepinephrine was within normal limits. It was increased in class III (1.6 times) and IV (2.4 times) patients. All patients received angiotensin-converting enzyme inhibitors, and their plasma renin activity and aldosterone varied greatly. In class IV patients, the mean values for renin activity and aldosterone were 76 and 5.1 times those of healthy subjects, respectively. Plasma concentration of ANP was higher than the normal range for our laboratory (22±20 pg/mL) in class II (3 times), III (5.6 times), and IV (9.1 times) patients. Nine patients of class IV died within 1 month after entry into the study. This indicates that the group of patients with severe CHF we studied was a group of preterminal patients, not representative of all class IV patients.
Serum TNF-
Individual levels of bioactive and antigenic
(ELISA) TNF- are
reported in Fig 1A and 1B). When measured by
bioassay,
TNF- was below the detection limit of our assay (<100 pg/mL) (Fig
1A). In the sera of 12 patients and of 5 healthy subjects, a
cytolytic
bioactivity was detectable. However, this cytotoxic effect was
unrelated to TNF-, since a rabbit polyclonal antibody against
rhTNF- added to these samples failed to inhibit their cytolytic
effect on L-M cells.
|
When the more sensitive ELISA method was used in
class IV, preterminal,
patients, the mean values of TNF- were higher than in healthy
subjects, with a degree of overlapping (from 14.33±7.08 to
33.52±13.12 pg/mL, P<.001). In class II and III patients,
mean values of TNF- were practically the same as normal values.
Serum sTNF-Rs
In class IV patients, both sTNF-Rs were higher
(P<.001) than in healthy subjects (3.8 times for the
sTNF-RI and 3.4 times for sTNF-RII) (Fig 1C and
1D). In class II and
III patients, the mean values of sTNF-Rs were not different from those
of control subjects but were significantly lower (P<.001)
than those of class IV patients.
Ten patients died within 1 month (mean
time to death, 13.7±8.2
days) after TNF determination. Nine were in class IV and one in class
III. Fig 2B and 2C shows that these patients had
significantly higher levels of antigenic TNF- (P<.05)
and of sTNF-Rs (P<.001). The same was not true for
norepinephrine, ANP (Fig 2D and 2E), renin
activity, and
aldosterone (data not shown). There was a correlation
between sTNF-RII values and duration of survival (r=.67,
P<.05). The discriminant stepwise analysis of all
parameters considered in this study showed that sTNF-RII
was the most important single independent variable predicting death
(F[1, 29]=86.24, 96% prediction of outcome). The other
parameters, included NYHA clinical classification, had a
lower value of predictivity (F[1, 29]<40).
|
Two of the 10
patients in class IV deteriorated substantially
immediately after entry into the study. In these patients, we were able
to monitor the TNF system every day for 4 and 5 days, respectively, up
until the time they died. The data are reported in Fig 3. In
both patients, TNF- bioactivity remained
undetectable. The antigenic TNF- varied widely. sTNF-Rs
progressively increased (sTNF-RI from 2.2 to 4.6 ng/mL and sTNF-RII
from 2.1 to 15.8 ng/mL in patient 1; sTNF-RI from 3.1 to 7.9 ng/mL and
sTNF-RII from 4.0 to 10.9 ng/mL in patient 2).
|
Addition of rhTNF-
to the serum of either healthy volunteers or
patients with mild to moderate CHF (classes II and III) resulted in a
106±66% (from 625 to 1290±411 pg/mL, P<.001) and
40±21% (from 625 to 877±132 pg/mL, P<.001) increase,
respectively, of the expected cytotoxic activity (Table 2).
Conversely, the same addition of rhTNF- to the
serum of preterminal patients with severe CHF (class IV) resulted
either in a complete inhibition of cytotoxic activity (4 patients) or
in a 58±32% (from 625 to 263±198 pg/mL, P<.001)
reduction of the expected cytotoxicity (Table 2).
|
Correlations
Table 3 and Fig 4
show the various
correlations between antigenic TNF-, sTNF-Rs, and other
parameters measured in this study.
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Our data suggest that the TNF system is activated in preterminal patients with heart failure in the absence of "cardiac cachexia," defined as a generalized wasting syndrome with a weight loss of at least 15% to 20% of the ideal body weight.19 20 The activation of the TNF system is complex, however, and measurement of sTNF-Rs is necessary to assess it fully. Antigenic TNF-
showed a great variability and, as a mean value, was
significantly increased in patients with severe CHF, confirming
previously reported data.2 3 5 Bioactive
TNF-, measured
by a cytolytic assay based on L-M cells, was undetectable in most of
the patients. Although the serum of some class II and III patients (12
of 37) was toxic to these cells, we were unable to neutralize these
effects with a polyclonal rabbit antiserum specific for TNF-,
suggesting that the cytotoxic activity was not related to TNF-. It
follows that we were unable to detect bioactive TNF- in any of the
patients studied. Sindhwani et al5 reported an increase of
bioactive TNF- in patients with severe CHF (14±6 U/mL) in the
presence of antigenic levels of TNF- (48±8 pg/mL), very close to
those we found. Similarly, Levine et al1 reported an
increase (>39 U/mL) of TNF- bioactivity on L-929 cells in patients
with CHF and cachexia. Taking into consideration the modest increase of
antigenic TNF- in our patients and the detection limit of our assay
(<100 pg/mL), we cannot exclude that an increase of TNF bioactivity
occurred in our patients as well. A further analysis using a
bioassay with higher sensitivity is necessary to clarify this
point.
However, it has been suggested that the bioactivity of TNF- in the
serum could be modulated by sTNF-Rs.11 12
Interestingly,
circulating sTNF-Rs were unchanged in our patients with mild and
moderate CHF but clearly elevated in class IV, preterminal, patients,
supporting the hypothesis that bioactivity of TNF- was modulated by
the increased levels of the soluble receptors, which directly bind to
the TNF- molecule or prevent its binding to cell receptors.
This latter hypothesis is supported by our data, which show that the
addition of rhTNF- to the serum of these patients with high levels
of sTNF-Rs reduced and, in some cases, completely inhibited the
expected TNF- bioactivity. Conversely, the addition of the same dose
of rhTNF- to the sera of healthy subjects or patients with less
severe cardiac failure (classes II and III) resulted in an increase of
the expected TNF- bioactivity. There was a correlation between
absolute levels of sTNF-Rs and the percent potentiation-inhibition
changes after spiking. This finding suggests that sTNF-Rs can inversely
modulate TNF- activity, depending on the circulating concentration
and time of exposure, providing an idea about the complexity of the TNF
system.
TNF- is produced by inflammatory cells and is a mediator of systemic
responses to sepsis and injury. It induces a cascade of
endogenous mediators involved in several immunological
functions.21 Thus, on the one hand, TNF- may be
considered an essential element in host defense against injury. On the
other, its excessive production mediates detrimental systemic
and cardiac effects and precipitates a syndrome similar to that of
septic shock and cachexia.22
sTNF-Rs, the naturally occurring inhibitors of TNF-
activity, can exert a counteraction that could be either advantageous
or injurious for the organism. When present in the serum at
physiological levels, they can protect trimeric
TNF- from monomerization and subsequent inactivation or can prolong
the half-life of circulating TNF.11 Hypothetically,
sTNF-Rs could have exerted this protective action in healthy subjects
or in patients with moderate CHF. This would explain the increase in
the expected activity that we found after the in vitro spiking with
rhTNF- of the serum of this population.
It has been shown that at physiological concentrations, sTNF-Rs may act as a "slow-release reservoir" of bioactive TNF, thus increasing its half-life.11 12 The mechanism for the spontaneous denaturation of TNF and the way it is inhibited by the sTNF-Rs are not understood. The stabilization of TNF by its soluble receptors is reminiscent of the stabilization of enzymes by their substrates. In both interactions, stabilization of the protein may be due to an induced conformational change that, in the case of TNF-Rs, is likely to occur in the extracellular, ligand-binding domains of the receptors.
When present at higher concentrations, as in our group of
preterminal patients in class IV, sTNF-Rs could inhibit the
pathological increase of TNF- activity. We observed inhibition of
the expected activity in class IV patients after addition of rhTNF-.
Under these conditions, sTNF-Rs could act as anti-TNF molecules by
forming complexes with high affinity to the
cytokine.11 12 The shedding of these receptors and
the resultant decrease in their concentration on the cell surface could
also prevent cell damage. Administration of sTNF-Rs to experimental
animals protects against shock and mortality induced by the TNF-
challenge.23 24 Alternatively, since TNF-
induces the
shedding of its soluble receptors, it is also possible that increased
sTNF-Rs simply reflect activation of the cytokine at a local
level. In this latter case, sTNF-Rs could be sensitive "serum
markers" of local TNF- activation. Interestingly, there was a
positive correlation between antigenic TNF- and sTNF-Rs.
It is known that the levels of sTNF-Rs correlate with the severity of
various
diseases.25 26 27 28 29
This was also true in our small
group of patients with CHF and particularly so for levels of sTNF-RII
associated with a short-term prognosis. This is not surprising, since
the levels of sTNF-RII were strongly correlated with natremia, ejection
fraction, cardiac index, right atrial pressure,
norepinephrine, and ANP, which from large-scale trials
appear to be prognostic factors for CHF. The stepwise discriminant
analysis showed that sTNF-RII was the most important single
independent variable in predicting death, better than the clinical
classification (NYHA). There are, however, several limitations for
considering sTNF-RII a prognostic indicator for CHF. First, the number
of patients we studied was very limited. Second, we analyzed
plasma levels of TNF- and sTNF-Rs at a given moment in time. We did
not investigate the biological turnover or the dynamic behavior of the
system. This limits the pathophysiological
significance of our findings, since, for example, the rate of shedding
of sTNF-Rs could be normal but their metabolic turnover or
renal clearance slowed in the terminal stages of heart failure. Third,
it is not clear at the moment whether the increase of sTNF-RII
concentration is a casual phenomenon or whether the complex of TNF-
and sTNF-RII has a direct pathological effect. Fourth, our patients in
class IV were preterminal and not representative of all
class IV patients.
We conclude that measurement of sTNF-Rs in addition to that of
antigenic and bioactive TNF- is essential for evaluation of the TNF
system in CHF. Both sTNF-RI and sTNF-RII are increased in preterminal
patients with severe heart failure and might modulate the in vitro
cytotoxicity of TNF-. Antigenic TNF- also increases in severe
CHF. The increase of sTNF-Rs, and particularly that of sTNF-RII,
correlates with poor prognosis. At present, it is not clear whether
the elevation of sTNF-Rs in terminal failure is due to an actual
increase or to a reduced breakdown or elimination of these receptors.
Further explorations are needed to more precisely define the meaning,
molecular basis, and interaction of sTNF-Rs and TNF- in CHF.
|
|
Acknowledgments |
|---|
This study was supported by National Research Council (CNR) target project "Prevention and Control Disease Factors" 93.00656 PF 41/115.19070 and by CNR target project "Biotechnology and Bioinstrumentation." Monoclonal antibodies 7H3 and 9B11 were produced under a National Research Program on Advanced Biotechnology contract stipulated by Tecnogen with the Italian Ministry of Research and Technology. The authors thank Tamara Bettini for technical assistance and Roberta Bonetti for secretarial assistance in preparing the manuscript. We thank Dr Marco Pagani for statistical analysis of the data and Dr Bill Dotson Smith for his editing of the manuscript.
Received November 1, 1994; revision received February 16, 1995; accepted February 25, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990;323:236-241. [Abstract]
2.
McMurray J, Abdullah I, Dargie HJ, Shapiro D.
Increased concentrations of tumor necrosis factor in
'cachectic' patients with severe chronic heart failure.
Br Heart J. 1991;66:356-358.
3.
Dutka DP, Elborn JS, Delamere F, Shale DJ, Morris GK.
Tumor necrosis factor in severe congestive cardiac
failure. Br Heart J. 1993;70:141-143.
4.
Katz SD, Rao R, Berman JW, Schwarz M, Demopoulos L,
Bijou R, LeJemtel TH. Pathophysiological
correlates of increased serum tumor necrosis factor in patients with
congestive heart failure: relation to nitric oxide-dependent
vasodilation in the forearm circulation.
Circulation. 1994;90:12-16.
5. Sindhwani R, Yuen J, Hirsch H, Tedguy A, Galvao M, Levato P, LeJemtel TH. Reversal of low flow state attenuates immune activation in severely decompensated congestive heart failure. Circulation. 1993;88(pt 2):I-255. Abstract.
6. Ruff MR, Gifford GE. Purification and physico-chemical characterization of rabbit tumor necrosis factor. J Immunol. 1980;125:1671-1677. [Abstract]
7. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55-63. [Medline] [Order article via Infotrieve]
8. Tartaglia LA, Goeddel DV. Two TNF receptors. Immunol Today. 1992;13:151-153. [Medline] [Order article via Infotrieve]
9. Smith CA, Farrah T, Goodwin RG. The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell. 1994;76:959-962. [Medline] [Order article via Infotrieve]
10.
Engelmann H, Aderka D, Rubinstein M, Rotman D, Wallach
D. A tumor necrosis factor–binding protein purified to
homogeneity from human urine protects cells from tumor necrosis factor
toxicity. J Biol Chem. 1989;264:11974-11980.
11.
Aderka D, Engelmann H, Maor Y, Brakebusch C, Wallach D.
Stabilization of the bioactivity of tumor necrosis factor by its
soluble receptors. J Exp Med. 1992;175:323-329.
12.
De Groote D, Grau GE, Dehart I, Franchimont P.
Stabilization of functional tumor necrosis factor- by its
soluble TNF receptors. Eur Cytokine Netw. 1993;4:359-362. [Medline]
[Order article via Infotrieve]
13.
Anand IS, Ferrari R, Kalra GS, Wahi PL, Poole-Wilson
PA, Harris P. Edema of cardiac origin: studies of body water and
sodium, renal function, hemodynamic indexes, and plasma
hormones in untreated congestive cardiac failure.
Circulation. 1989;80:299-305.
14. Ceconi C, Condorelli E, Quinzanini M, Rodella A, Ferrari R, Harris P. Noradrenaline, atrial natriuretic peptide, bombesin and neurotensin in myocardium and blood of rats in congestive cardiac failure. Cardiovasc Res. 1989;23:674-682. [Medline] [Order article via Infotrieve]
15. Ferrari R, Anand IS, Kalra GS, Wahi PL, Poole-Wilson PA, Harris P. Body fluid compartments, renal function, hormone levels and hemodynamics in untreated congestive heart failure. Circulation. 1988;28:106. Abstract.
16.
Poiesi C, Rodella A, Mantero G, Cannella G, Ferrari R,
Albertini A. Improved radioimmunoassay of atrial
natriuretic peptide in plasma. Clin
Chem. 1989;35:1431-1434.
17.
Nargi FE, Yang TJ. Optimization of the L-M cell
bioassay for quantitating tumor necrosis factor in serum and
plasma. J Immunol Methods. 1993;159:81-91. [Medline]
[Order article via Infotrieve]
18.
Corti A, Bagnasco L, Cassani G. Identification
of an epitope of tumor necrosis factor (TNF)-receptor type I (P55)
recognized by a TNF- antagonist monoclonal
antibody. Lymphokine Cytokine Res. 1994;13:183-190. [Medline]
[Order article via Infotrieve]
19. Ansari A. Syndromes of cardiac cachexia and the cachectic heart: current perspective. Prog Cardiovasc Dis. 1987;30:45-60. [Medline] [Order article via Infotrieve]
20. Morrison WL, Edwards RHT. Cardiac cachexia. BMJ. 1991;302:301-302.
21. Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411-452. [Medline] [Order article via Infotrieve]
22. van Deuren M, Dofferhoff ASM, van der Meer JWM. Cytokines and the response to infection. J Pathol. 1992;168:349-356. [Medline] [Order article via Infotrieve]
23. Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, Lowry SF, Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987;330:662-664. [Medline] [Order article via Infotrieve]
24. Mohler KM, Torrance DS, Smith CA, Goodwin RG, Stremler KE, Fung VP, Madani H, Widmer MB. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol. 1993;151:1548-1561. [Abstract]
25. Gruss HJ, Dolken G, Brach MA, Mertelsmann R, Herrmann F. The significance of serum levels of soluble 60kDa receptors for tumor necrosis factor in patients with Hodgkin's disease. Leukemia. 1993;7:1339-1343. [Medline] [Order article via Infotrieve]
26. Aderka D, Wysenbeek A, Engelmann H, Cope AP, Brennan F, Molad Y, Hornik V, Levo Y, Maini RN, Feldmann M, Wallach D. Correlation between serum levels of soluble tumor necrosis factor receptors and disease activity in systemic lupus erythematosus. Arthritis Rheum. 1993;36:1111-1120. [Medline] [Order article via Infotrieve]
27. Barrera P, Boerbooms AM, Janssen EM, Sauerwein RW, Gallati H, Mulder J, de Boo T, Demacker PN, van de Putte LB, van der Meer JW. Circulating soluble tumor necrosis factor receptors, interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-6 levels in rheumatoid arthritis: longitudinal evaluation during methotrexate and azathioprine therapy. Arthritis Rheum. 1993;36:1070-1079. [Medline] [Order article via Infotrieve]
28. Aukrust P, Liabakk NB, Muller F, Lien E, Espevik T, Froland SS. Serum levels of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in human immunodeficiency virus type 1 infection: correlations to clinical, immunologic, and virologic parameters. J Infect Dis. 1994;169:420-424. [Medline] [Order article via Infotrieve]
29. Zangerle R, Gallati H, Sarcletti M, Weiss G, Denz H, Wachter H, Fuchs D. Increased serum concentrations of soluble tumor necrosis factor receptors in HIV-infected individuals are associated with immune activation. J Acquir Immune Defic Syndr. 1994;7:79-85.
This article has been cited by other articles:
 |
|
 |
|
  C. Bergamini, M. Cicoira, A. Rossi, and C. Vassanelli Oxidative stress and hyperuricaemia: pathophysiology, clinical relevance, and therapeutic implications in chronic heart failure Eur J Heart Fail, May 1, 2009; 11(5): 444 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Arias, F. Garcia-Rio, A. Alonso-Fernandez, A. Hernanz, R. Hidalgo, V. Martinez-Mateo, S. Bartolome, and L. Rodriguez-Padial CPAP decreases plasma levels of soluble tumour necrosis factor-{alpha} receptor 1 in obstructive sleep apnoea Eur. Respir. J., October 1, 2008; 32(4): 1009 - 1015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Han, T. R. Hansen, B. Berg, B. W. Hess, and S. P. Ford Maternal undernutrition induces differential cardiac gene expression in pulmonary hypertensive steers at high elevation Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H382 - H389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pignatelli, R. Cangemi, A. Celestini, R. Carnevale, L. Polimeni, A. Martini, D. Ferro, L. Loffredo, and F. Violi Tumour necrosis factor {alpha} upregulates platelet CD40L in patients with heart failure Cardiovasc Res, June 1, 2008; 78(3): 515 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Banfi, M. Brioschi, S. Barcella, F. Veglia, P. Biglioli, E. Tremoli, and P. Agostoni Oxidized proteins in plasma of patients with heart failure: Role in endothelial damage Eur J Heart Fail, March 1, 2008; 10(3): 244 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Crippa, A. Gasparri, A. Sacchi, E. Ferrero, F. Curnis, and A. Corti Synergistic Damage of Tumor Vessels with Ultra Low-Dose Endothelial-Monocyte Activating Polypeptide-II and Neovasculature-Targeted Tumor Necrosis Factor-{alpha} Cancer Res., February 15, 2008; 68(4): 1154 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Metyas, D La, and D G Arkfeld The use of the tumour necrosis factor antagonist infliximab in heart transplant recipients: two case reports Ann Rheum Dis, November 1, 2007; 66(11): 1544 - 1545. [Full Text] [PDF]
|
|
|
|
|
|
S. von Haehling, W. Doehner, and S. D Anker Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure Cardiovasc Res, January 15, 2007; 73(2): 298 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Trikas, C. Antoniades, G. Latsios, K. Vasiliadou, I. Karamitros, D. Tousoulis, C. Tentolouris, and C. Stefanadis Long-term effects of levosimendan infusion on inflammatory processes and sFas in patients with severe heart failure Eur J Heart Fail, December 1, 2006; 8(8): 804 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bauersachs, K. Hiss, D. Fraccarollo, U. Laufs, and H. Ruetten Simvastatin improves left ventricular function after myocardial infarction in hypercholesterolemic rabbits by anti-inflammatory effects Cardiovasc Res, December 1, 2006; 72(3): 438 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wohlschlaeger, K. J. Schmitz, C. Schmid, K. W. Schmid, P. Keul, A. Takeda, S. Weis, B. Levkau, and H. A. Baba Reverse remodeling following insertion of left ventricular assist devices (LVAD): A review of the morphological and molecular changes Cardiovasc Res, December 1, 2005; 68(3): 376 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bruunsgaard Physical activity and modulation of systemic low-level inflammation J. Leukoc. Biol., October 1, 2005; 78(4): 819 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Varol, M. Ozaydin, A. Dogan, and F. Kosar Tumour marker levels in patients with chronic heart failure Eur J Heart Fail, August 1, 2005; 7(5): 840 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. George, S. Patal, D. Wexler, A. Abashidze, H. Shmilovich, T. Barak, D. Sheps, and G. Keren Circulating Erythropoietin Levels and Prognosis in Patients With Congestive Heart Failure: Comparison With Neurohormonal and Inflammatory Markers Arch Intern Med, June 13, 2005; 165(11): 1304 - 1309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Niebauer, A. L. Clark, K. M. Webb-Peploe, and A. J.S. Coats Exercise training in chronic heart failure: effects on pro-inflammatory markers Eur J Heart Fail, March 2, 2005; 7(2): 189 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Valgimigli, C. Ceconi, P. Malagutti, E. Merli, O. Soukhomovskaia, G. Francolini, G. Cicchitelli, A. Olivares, G. Parrinello, G. Percoco, et al. Tumor Necrosis Factor-{alpha} Receptor 1 Is a Major Predictor of Mortality and New-Onset Heart Failure in Patients With Acute Myocardial Infarction: The Cytokine-Activation and Long-Term Prognosis in Myocardial Infarction (C-ALPHA) Study Circulation, February 22, 2005; 111(7): 863 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Curtis, J. G. Selter, Y. Wang, S. S. Rathore, I. S. Jovin, F. Jadbabaie, M. Kosiborod, E. L. Portnay, S. I. Sokol, F. Bader, et al. The Obesity Paradox: Body Mass Index and Outcomes in Patients With Heart Failure Arch Intern Med, January 10, 2005; 165(1): 55 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Wisniacki, W Taylor, M Lye, and J P H Wilding Insulin resistance and inflammatory activation in older patients with systolic and diastolic heart failure Heart, January 1, 2005; 91(1): 32 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Faggiano, A. D'Aloia, L. Brentana, T. Bignotti, C. Fiorina, E. Vizzardi, and L. D. Cas Serum levels of different tumour markers in patients with chronic heart failure Eur J Heart Fail, January 1, 2005; 7(1): 57 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rivera, R. Talens-Visconti, R. Sirera, V. Bertomeu, A. Salvador, R. Cortes, F. G. de Burgos, V. Climent, R. Paya, L. Martinez-Dolz, et al. Soluble TNF-{alpha} and interleukin-6 receptors in the urine of heart failure patients. Their clinical value and relationship with plasma levels Eur J Heart Fail, December 1, 2004; 6(7): 877 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Bachetti, L. Comini, E. Pasini, and R. Ferrari Anti-cytokine therapy in chronic heart failure: new approaches and unmet promises Eur. Heart J. Suppl., November 1, 2004; 6(suppl_F): F16 - F21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Patrianakos, F. I. Parthenakis, E. A. Papadimitriou, G. F. Diakakis, P. G. Tzerakis, D. Nikitovic, and P. E. Vardas Restrictive filling pattern is associated with increased humoral activation and impaired exercise capacity in dilated cardiomyopathy Eur J Heart Fail, October 1, 2004; 6(6): 735 - 743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Valgimigli, E. Merli, P. Malagutti, O. Soukhomovskaia, G. Cicchitelli, A. Antelli, D. Canistro, G. Francolini, G. Macri, F. Mastrorilli, et al. Hydroxyl radical generation, levels of tumor necrosis factor-alpha, and progression to heart failure after acute myocardial infarction J. Am. Coll. Cardiol., June 2, 2004; 43(11): 2000 - 2008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Krack, B. M. Richartz, A. Gastmann, K. Greim, U. Lotze, S. D. Anker, and H. R. Figulla Studies on intragastric PCO2 at rest and during exercise as a marker of intestinal perfusion in patients with chronic heart failure Eur J Heart Fail, June 1, 2004; 6(4): 403 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Conraads, P. G. Jorens, L. S. De Clerck, H. K. Van Saene, M. M. Ieven, J. M. Bosmans, A. Schuerwegh, C. H. Bridts, F. Wuyts, W. J. Stevens, et al. Selective intestinal decontamination in advanced chronic heart failure: a pilot trial Eur J Heart Fail, June 1, 2004; 6(4): 483 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Higuchi, C. F. McTiernan, C. B. Frye, B. S. McGowan, T. O. Chan, and A. M. Feldman Tumor Necrosis Factor Receptors 1 and 2 Differentially Regulate Survival, Cardiac Dysfunction, and Remodeling in Transgenic Mice With Tumor Necrosis Factor-{alpha}-Induced Cardiomyopathy Circulation, April 20, 2004; 109(15): 1892 - 1897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, H. Wang, Y. Zhang, H. Gao, S. Nattel, and Z. Wang Impairment of HERG K+ Channel Function by Tumor Necrosis Factor-{alpha}: ROLE OF REACTIVE OXYGEN SPECIES AS A MEDIATOR J. Biol. Chem., April 2, 2004; 279(14): 13289 - 13292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mozaffarian, T. Pischon, S. E Hankinson, N. Rifai, K. Joshipura, W. C Willett, and E. B Rimm Dietary intake of trans fatty acids and systemic inflammation in women Am. J. Clinical Nutrition, April 1, 2004; 79(4): 606 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Athanassopoulos, L. M.B. Vaessen, A. P.W.M. Maat, A. H.M.M. Balk, W. Weimar, and A. J.J.C. Bogers Peripheral blood dendritic cells in human end-stage heart failure and the early post-transplant period: evidence for systemic Th1 immune responses Eur. J. Cardiothorac. Surg., April 1, 2004; 25(4): 619 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D Anker and S. von Haehling Inflammatory mediators in chronic heart failure: an overview Heart, April 1, 2004; 90(4): 464 - 470. [Full Text] [PDF]
|
|
|
|
 |
|
 V. M. Conraads, J. M. Bosmans, A. J. Schuerwegh, L. S. De Clerck, C. H. Bridts, F. L. Wuyts, W. J. Stevens, and C. J. Vrints Association of lipoproteins with cytokines and cytokine receptors in heart failure patients: Differences between ischaemic versus idiopathic cardiomyopathy Eur. Heart J., December 2, 2003; 24(24): 2221 - 2226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Aker, S. Belosjorow, I. Konietzka, A. Duschin, C. Martin, G. Heusch, and R. Schulz Serum but not myocardial TNF-{alpha} concentration is increased in pacing-induced heart failure in rabbits Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R463 - R469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Pischon, S. E. Hankinson, G. S. Hotamisligil, N. Rifai, W. C. Willett, and E. B. Rimm Habitual Dietary Intake of n-3 and n-6 Fatty Acids in Relation to Inflammatory Markers Among US Men and Women Circulation, July 15, 2003; 108(2): 155 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D'Aloia, P. Faggiano, G. Aurigemma, L. Bontempi, G. Ruggeri, M. Metra, S. Nodari, and L. Dei Cas Serum levels of carbohydrate antigen 125 in patients with chronic heart failure: Relation to clinical severity, hemodynamic and Doppler echocardiographic abnormalities, and short-term prognosis J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1805 - 1811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pasic, W. C. Levy, and M. D. Sullivan Cytokines in Depression and Heart Failure Psychosom Med, March 1, 2003; 65(2): 181 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Valgimigli, L. Agnoletti, S. Curello, L. Comini, G. Francolini, F. Mastrorilli, E. Merli, R. Pirani, G. Guardigli, P. G. Grigolato, et al. Serum From Patients With Acute Coronary Syndromes Displays a Proapoptotic Effect on Human Endothelial Cells: A Possible Link to Pan-Coronary Syndromes Circulation, January 21, 2003; 107(2): 264 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V.M. Conraads, P. Beckers, J. Bosmans, L.S. De Clerck, W.J. Stevens, C.J. Vrints, and D.L. Brutsaert Combined endurance/resistance training reduces plasma TNF-{alpha} receptor levels in patients with chronic heart failure and coronary artery disease Eur. Heart J., December 1, 2002; 23(23): 1854 - 1860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Pugh, R. D. Jones, T.H. Jones, and K. S. Channer Heart failure as an inflammatory condition: potential role for androgens as immune modulators Eur J Heart Fail, December 1, 2002; 4(6): 673 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.B. Felix, A. Staudt, and G. Baumann Immunoadsorption as a new therapeutic principle for treatment of dilated cardiomyopathy Eur. Heart J. Suppl., December 1, 2002; 4(suppl_I): I63 - I68. [Abstract] [PDF]
|
|
|
|
 |
|
 B. J. Holycross and M. J. Radin Cytokines in Heart Failure: Potential Interactions with Angiotensin II and Leptin Mol. Interv., November 1, 2002; 2(7): 424 - 427. [Abstract] [Full Text]
|
|
|
|
|
|
G. Vescovo, B. Ravara, A. Angelini, M. Sandri, U. Carraro, C. Ceconi, and L. D. Libera Effect of thalidomide on the skeletal muscle in experimental heart failure Eur J Heart Fail, August 1, 2002; 4(4): 455 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ceconi, R. Ferrari, T. Bachetti, C. Opasich, M. Volterrani, B. Colombo, G. Parrinello, and A. Corti Chromogranin A in heart failure. A novel neurohumoral factor and a predictor for mortality Eur. Heart J., June 2, 2002; 23(12): 967 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.L. Alonso-Martinez, B. Llorente-Diez, M. Echegaray-Agara, F. Olaz-Preciado, M. Urbieta-Echezarreta, and C. Gonzalez-Arencibia C-reactive protein as a predictor of improvement and readmission in heart failure Eur J Heart Fail, June 1, 2002; 4(3): 331 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. S. Bradham, B. Bozkurt, H. Gunasinghe, D. Mann, and F. G. Spinale Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective Cardiovasc Res, March 1, 2002; 53(4): 822 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Adamopoulos, J. Parissis, D. Karatzas, C. Kroupis, M. Georgiadis, G. Karavolias, J. Paraskevaidis, K. Koniavitou, A. J. S. Coats, and D. T. Kremastinos Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fasligand system in patients with chronic heart failure J. Am. Coll. Cardiol., February 20, 2002; 39(4): 653 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ferrari Interleukin-6: a neurohumoral predictor of prognosis in patients with heart failure: light and shadow Eur. Heart J., January 1, 2002; 23(1): 9 - 10. [Full Text] [PDF]
|
|
|
|
|
|
A.L. Clark, M. Loebe, E.V. Potapov, K. Egerer, C. Knosalla, R. Hetzer, and S.D. Anker Ventricular assist device in severe heart failure. Effects on cytokines, complement and body weight Eur. Heart J., December 2, 2001; 22(24): 2275 - 2283. [Abstract] [PDF]
|
|
|
|
|
|
A. P. Bolger, R. Sharma, P. Aukrust, L. Gullestad, H. Aass, J. G. Fjeld, L. Wikeby, A. K. Andreassen, H. Ihlen, S. Simonsen, et al. Increase in Anti-Inflammatory Cytokine Levels in Chronic Heart Failure: A Measure of Treatment Success or Failure? Response Circulation, October 30, 2001; 104 (18): e97 - e97. [Full Text] [PDF]
|
|
|
|
|
|
S. Adamopoulos, J. T. Parissis, and D. Th. Kremastinos A glossary of circulating cytokines in chronic heart failure Eur J Heart Fail, October 1, 2001; 3(5): 517 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Y. T. Hart, E. L. Hahn, D. M. Meyer, J. C. Burnett Jr., and M. M. Redfield Differential effects of natriuretic peptides and NO on LV function in heart failure and normal dogs Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H146 - H154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Dalla Libera, B. Ravara, A. Angelini, K. Rossini, M. Sandri, G. Thiene, G. Battista Ambrosio, and G. Vescovo Beneficial Effects on Skeletal Muscle of the Angiotensin II Type 1 Receptor Blocker Irbesartan in Experimental Heart Failure Circulation, May 1, 2001; 103(17): 2195 - 2200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Deswal, N. J. Petersen, A. M. Feldman, J. B. Young, B. G. White, and D. L. Mann Cytokines and Cytokine Receptors in Advanced Heart Failure : An Analysis of the Cytokine Database from the Vesnarinone Trial (VEST) Circulation, April 24, 2001; 103(16): 2055 - 2059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Graciano, D. D. Bryant, D. J. White, J. Horton, N. E. Bowles, and B. P. Giroir Targeted disruption of ICAM-1, P-selectin genes improves cardiac function and survival in TNF-{alpha} transgenic mice Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1464 - H1471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L.P. Caforio, J. H. Goldman, M. K. Baig, N. J. Mahon, A. J. Haven, B. E. Souberbielle, D. W. Holt, A. G. Dalgleish, and W. J. McKenna Elevated serum levels of soluble interleukin-2 receptor, neopterin and {beta}-2-microglobulin in idiopathic dilated cardiomyopathy: relation to disease severity and autoimmune pathogenesis Eur J Heart Fail, March 1, 2001; 3(2): 155 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ohtsuka, M. Hamada, G. Hiasa, O. Sasaki, M. Suzuki, Y. Hara, Y. Shigematsu, and K. Hiwada Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy J. Am. Coll. Cardiol., February 1, 2001; 37(2): 412 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rauchhaus, W. Doehner, D. P. Francis, C. Davos, M. Kemp, C. Liebenthal, J. Niebauer, J. Hooper, H.-D. Volk, A. J. S. Coats, et al. Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure Circulation, December 19, 2000; 102(25): 3060 - 3067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fuse, M. Kodama, Y. Okura, M. Ito, S. Hirono, K. Kato, H. Hanawa, and Y. Aizawa Predictors of Disease Course in Patients With Acute Myocarditis Circulation, December 5, 2000; 102(23): 2829 - 2835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rossig, J. Haendeler, Z. Mallat, B. Hugel, J.-M. Freyssinet, A. Tedgui, S. Dimmeler, and A. M. Zeiher Congestive heart failure induces endothelial cell apoptosis: protective role of carvedilol J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2081 - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Maeda, T. Tsutamoto, A. Wada, N. Mabuchi, M. Hayashi, T. Tsutsui, M. Ohnishi, M. Sawaki, M. Fujii, T. Matsumoto, et al. High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1587 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Bozkurt Activation of cytokines as a mechanism of disease progression in heart failure Ann Rheum Dis, November 1, 2000; 59(90001): i90 - 93. [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Kotler Cachexia Ann Intern Med, October 17, 2000; 133(8): 622 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Peri, M. Introna, D. Corradi, G. Iacuitti, S. Signorini, F. Avanzini, F. Pizzetti, A. P. Maggioni, T. Moccetti, M. Metra, et al. PTX3, A Prototypical Long Pentraxin, Is an Early Indicator of Acute Myocardial Infarction in Humans Circulation, August 8, 2000; 102(6): 636 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Bokesch, M. B. Kapural, E. B. Mossad, M. Cavaglia, E. Appachi, J. J. Drummond-Webb, and R. B.B. Mee Do peritoneal catheters remove pro-inflammatory cytokines after cardiopulmonary bypass in neonates? Ann. Thorac. Surg., August 1, 2000; 70(2): 639 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Kapadia, K. Yakoob, S. Nader, J. D. Thomas, D. L. Mann, and B. P. Griffin Elevated circulating levels of serum tumor necrosis factor-alpha in patients with hemodynamically significant pressure and volume overload J. Am. Coll. Cardiol., July 1, 2000; 36(1): 208 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Okuyama, S. Yamaguchi, M. Yamaoka, J. Nitobe, S. Fujii, T. Yoshimura, and H. Tomoike Nitric Oxide Enhances Expression and Shedding of Tumor Necrosis Factor Receptor I (p55) in Endothelial Cells Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1506 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R Gosker, E. F. Wouters, G. J van der Vusse, and A. M. Schols Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives Am. J. Clinical Nutrition, May 1, 2000; 71(5): 1033 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Felix, A. Staudt, W. V. Dorffel, V. Stangl, K. Merkel, M. Pohl, W. D. Docke, S. Morgera, H. H. Neumayer, K. D. Wernecke, et al. Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: Three-month results from a randomized study J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1590 - 1598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.P. Davey and H. Ashrafian New therapies for heart failure: is thalidomide the answer? QJM, May 1, 2000; 93(5): 305 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Berry and A.L Clark Catabolism in chronic heart failure Eur. Heart J., April 1, 2000; 21(7): 521 - 532. [PDF]
|
|
|
|
|
|
A. M. Feldman, A. Combes, D. Wagner, T. Kadakomi, T. Kubota, Y. You Li, and C. McTiernan The role of tumor necrosis factor in the pathophysiology of heart failure J. Am. Coll. Cardiol., March 1, 2000; 35(3): 537 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sliwa, D. Skudicky, A. Bergemann, G. Candy, A. Puren, and P. Sareli Peripartum cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1 J. Am. Coll. Cardiol., March 1, 2000; 35(3): 701 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tsutamoto, A. Wada, K. Maeda, N. Mabuchi, M. Hayashi, T. Tsutsui, M. Ohnishi, M. Sawaki, M. Fujii, T. Matsumoto, et al. Angiotensin II type 1 receptor antagonist decreases plasma levels of tumor necrosis factor alpha, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure J. Am. Coll. Cardiol., March 1, 2000; 35(3): 714 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Recchia, R. D. Bernstein, P. B. Sehgal, N. R. Ferreri, and T. H. Hintze Cytokines Are Not a Requisite Part of the Pathophysiology Leading to Cardiac Decompensation Experimental Biology and Medicine, January 1, 2000; 223(1): 47 - 52. [Abstract] [Full Text]
|
|
|
|
|
|
L. Agnoletti, S. Curello, T. Bachetti, F. Malacarne, G. Gaia, L. Comini, M. Volterrani, P. Bonetti, G. Parrinello, M. Cadei, et al. Serum From Patients With Severe Heart Failure Downregulates eNOS and Is Proapoptotic : Role of Tumor Necrosis Factor-{alpha} Circulation, November 9, 1999; 100(19): 1983 - 1991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Comini, T. Bachetti, L. Agnoletti, G. Gaia, S. Curello, B. Milanesi, M. Volterrani, G. Parrinello, C. Ceconi, A. Giordano, et al. Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-{alpha} Eur. Heart J., October 2, 1999; 20(20): 1503 - 1513. [Abstract] [PDF]
|
|
|
|
|
|
M. R. Bergman, R. H. Kao, S. A. McCune, and B. J. Holycross Myocardial tumor necrosis factor-alpha secretion in hypertensive and heart failure-prone rats Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H543 - H550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Francis TNF-{alpha} and Heart Failure : The Difference Between Proof of Principle and Hypothesis Testing Circulation, June 29, 1999; 99(25): 3213 - 3214. [Full Text] [PDF]
|
|
|
|
|
|
Z. Dibbs, J. Thornby, B. G. White, and D. L. Mann Natural variability of circulating levels of cytokines and cytokine receptors in patients with heart failure: implications for clinical trials J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1935 - 1942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W Moe and P. Armstrong Pacing-induced heart failure: a model to study the mechanism of disease progression and novel therapy in heart failure Cardiovasc Res, June 1, 1999; 42(3): 591 - 599. [Full Text] [PDF]
|
|
|
|
|
|
S.D. Anker, P.P. Ponikowski, A.L. Clark, F. Leyva, M. Rauchhaus, M. Kemp, M.M. Teixeira, P.G. Hellewell, J. Hooper, P.A. Poole-Wilson, et al. Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure Eur. Heart J., May 1, 1999; 20(9): 683 - 693. [Abstract] [PDF]
|
|
|
|
 |
|
 E. H. Herrera-Garza, S. J. Stetson, A. Cubillos-Garzon, M. T. Vooletich, J. A. Farmer, and G. Torre-Amione Tumor Necrosis Factor-{alpha}: A Mediator of Disease Progression in the Failing Human Heart Chest, April 1, 1999; 115(4): 1170 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Irwin, S. Mak, D. L. Mann, R. Qu, J. M. Penninger, A. Yan, F. Dawood, W.-H. Wen, Z. Shou, and P. Liu Tissue Expression and Immunolocalization of Tumor Necrosis Factor-{alpha} in Postinfarction Dysfunctional Myocardium Circulation, March 23, 1999; 99(11): 1492 - 1498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Anker and A. J. S. Coats Cardiac Cachexia: A Syndrome With Impaired Survival and Immune and Neuroendocrine Activation Chest, March 1, 1999; 115(3): 836 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. VERGHESE, K. MCCORMICK-SHANNON, R. J. MASON, and M. A. MATTHAY Hepatocyte Growth Factor and Keratinocyte Growth Factor in the Pulmonary Edema Fluid of Patients with Acute Lung Injury . Biologic and Clinical Significance Am. J. Respir. Crit. Care Med., August 1, 1998; 158(2): 386 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kubota, D. M. McNamara, J. J. Wang, M. Trost, C. F. McTiernan, D. L. Mann, and A. M. Feldman Effects of Tumor Necrosis Factor Gene Polymorphisms on Patients With Congestive Heart Failure Circulation, June 30, 1998; 97(25): 2499 - 2501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Haunstetter and S. Izumo Apoptosis : Basic Mechanisms and Implications for Cardiovascular Disease Circ. Res., June 15, 1998; 82(11): 1111 - 1129. [Full Text] [PDF]
|
|
|
|
|
|
D. Bryant, L. Becker, J. Richardson, J. Shelton, F. Franco, R. Peshock, M. Thompson, and B. Giroir Cardiac Failure in Transgenic Mice With Myocardial Expression of Tumor Necrosis Factor-{alpha} Circulation, April 14, 1998; 97(14): 1375 - 1381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Bozkurt, S. B. Kribbs, F. J. Clubb Jr, L. H. Michael, V. V. Didenko, P. J. Hornsby, Y. Seta, H. Oral, F. G. Spinale, and D. L. Mann Pathophysiologically Relevant Concentrations of Tumor Necrosis Factor-{alpha} Promote Progressive Left Ventricular Dysfunction and Remodeling in Rats Circulation, April 14, 1998; 97(14): 1382 - 1391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kubota, C. F. McTiernan, C. S. Frye, S. E. Slawson, B. H. Lemster, A. P. Koretsky, A. J. Demetris, and A. M. Feldman Dilated Cardiomyopathy in Transgenic Mice With Cardiac-Specific Overexpression of Tumor Necrosis Factor-{alpha} Circ. Res., October 19, 1997; 81(4): 627 - 635. [Abstract] [Full Text]
|
|
|
|
|
|
T. De Marco and L. Goldman Predicting Outcomes in Severe Heart Failure Circulation, June 17, 1997; 95(12): 2597 - 2599. [Full Text]
|
|
|
|
|
|
K. D. Aaronson, J. S. Schwartz, T.-M. Chen, K.-L. Wong, J. E. Goin, and D. M. Mancini Development and Prospective Validation of a Clinical Index to Predict Survival in Ambulatory Patients Referred for Cardiac Transplant Evaluation Circulation, June 17, 1997; 95(12): 2660 - 2667. [Abstract] [Full Text]
|
|
|
|
|
|
R. A. Kelly and T. W. Smith Cytokines and Cardiac Contractile Function Circulation, February 18, 1997; 95(4): 778 - 781. [Full Text]
|
|
|
|
|
|
M. Packer Is Tumor Necrosis Factor an Important Neurohormonal Mechanism in Chronic Heart Failure? Circulation, September 15, 1995; 92(6): 1379 - 1382. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||