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(Circulation. 2001;103:220.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Immunomodulating Therapy With Intravenous Immunoglobulin in Patients With Chronic Heart Failure
From the Department of Cardiology (L.G., H.A., A.K.A, H.I., S.S., J.K., S.N.-H.), Section of Endocrinology (T.U.), and Section of Clinical Immunology and Infectious Diseases (S.S.F., P.A.), Medical Department, Research Institute for Internal Medicine (S.S.F., P.A.), and Section of Nuclear Medicine (J.G.F.), Rikshospitalet, Oslo, Norway; and Institute of Cancer Research and Molecular Biology (E.L.), The Norwegian University of Science and Technology, Trondheim, Norway.
Correspondence to Pål Aukrust, MD, PhD, Section of Clinical Immunology and Infectious Diseases, Medical Department, Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway. E-mail pal.aukrust{at}rikshospitalet.no
Background—Congestive heart failure (CHF) is characterized by enhanced immune activation, and immune-mediated mechanisms may play a pathogenic role in this disorder. Based on the immunomodulatory effects of intravenous immunoglobulin (IVIG), we hypothesized that IVIG could downregulate inflammatory responses in CHF patients and have potential beneficial effects on the left ventricular ejection fraction (LVEF).
Methods and Results—Forty patients with chronic symptomatic CHF and LVEF of <40%, stratified according to cause (ie, ischemic and idiopathic dilated cardiomyopathy), were randomized in a double-blind fashion to receive therapy with IVIG or placebo for a total period of 26 weeks. Our main findings were that (1) IVIG, but not placebo, induced a marked rise in plasma levels of the anti-inflammatory mediators interleukin (IL)-10, IL-1 receptor antagonist, and soluble tumor necrosis factor receptors; (2) significantly correlated with these anti-inflammatory effects, IVIG, but not placebo, induced a significant increase in LVEF from 26±2% to 31±3% (P<0.01), and this was found independent of the cause of heart failure; and (3) N-terminal pro–atrial natriuretic peptide decreased significantly after induction therapy and continued to decrease toward the end of study during IVIG therapy (P<0.001) but remained unchanged during placebo.
Conclusions—We demonstrated an IVIG-induced change in the balance between inflammatory and anti-inflammatory cytokines that favored an anti-inflammatory net effect in CHF. This effect was significantly correlated with an improvement in LVEF, suggesting a potential for immunomodulating therapy in addition to optimal conventional cardiovascular treatment regimens in CHF patients.
Key Words: heart failure • inflammation • interleukins • immune system
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