(Circulation. 1997;96:3042-3047.)
© 1997 American Heart Association, Inc.
Articles |
Inflammatory Cytokines Impair Endothelium-Dependent Dilatation in Human Veins In Vivo
From the Centre for Clinical Pharmacology, Cruciform Project for Strategic Medical Research and Department of Medicine, University College London (UK).
Correspondence to Kiran Bhagat, BSc, PhD, MRCP, Centre for Clinical Pharmacology, University College London, London, UK. E-mail k.bhagat{at}ucl.ac.uk
Background Endothelial dysfunction occurs in many diseases associated with increased cardiovascular risk. We examined the effects of pro-inflammatory cytokines on endothelial function.
Methods and Results Subjects lay with one hand placed on an
angled support. The diameter of a vein was recorded by measuring
the linear displacement of a probe placed on the skin overlying the
vein when the pressure in a congesting cuff placed around the upper arm
was deflated from 40 to 0 mm Hg. A length of the vein was
isolated by two wedges. TNF-
(1 ng), IL-1ß (1 ng), or IL-6 (100
pg) were instilled for 1 hour, either individually or together. At the
end of the hour, the wedges were removed and the vein reconnected with
the circulation. Dose-response curves (bradykinin: 2, 4, and 8
pmol/min; arachidonic acid: 0.2, 2, and 20 nmol/min;
and glyceryl trinitrate 1, 2, and 4 pmol/min) were constructed before
and 1, 6, 24, and 48 hours after instillation. In another study,
hydrocortisone (100 mg) was given 2 hours before the study. In a
different study, subjects were given oral aspirin (75 mg or 1 g) 2
hours before the study. TNF- and IL-1ß alone but not IL-6
attenuated the dilatation to bradykinin and arachidonic
acid; the response was greatest at 1 hour with recovery occurring by 6
hours. Combination of IL-1ß and TNF- prolonged the
endothelial dysfunction, resulting in recovery at 24
hours. Hydrocortisone and high-dose aspirin prevented
endothelial dysfunction.
Conclusions The results demonstrate that pro-inflammatory cytokines induce transient and reversible endothelial dysfunction and indicate that cyclooxygenase activity may contribute to the genesis of the effect. If other vessels behave similarly, this may provide further insight into the mechanisms precipitating acute cardiovascular events after inflammatory disorders.
Key Words: endothelium • vasodilation • bradykinin • interleukins • prostaglandins
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