AJP - Lung Cellular and Molecular Physiology, Vol 264, Issue 2 175-L182, Copyright © 1993 by American Physiological Society
Effect of PAF receptor antagonism on cardiopulmonary alterations during coinfusion of TNF-alpha and IL-1 alpha in pigs
K. T. Kruse-Elliott, M. V. Pino and N. C. Olson
Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
We examined the possibility that platelet-activating factor (PAF) might be
a mediator of cardiopulmonary alterations induced by a 6-h coinfusion of
human recombinant tumor necrosis factor (TNF-alpha) and interleukin-1 alpha
(IL-1 alpha) in anesthetized pigs. Our hypothesis was tested by pretreating
TNF-alpha + IL-1 alpha-infused pigs with WEB 2086 (3 mg/kg from -0.5 to 0 h
+ 0.75 mg.kg-1.h-1 from 0-6 h), a specific PAF receptor antagonist. Each
cytokine was infused intravenously at 0.5 microgram/kg from 0-0.5 h + 5
ng.kg-1.min-1 from 0.5-6 h. WEB 2086 attenuated the early (0.25 h)
cytokine-induced increases in mean pulmonary arterial pressure and
pulmonary vascular resistance and blocked or markedly attenuated the later
occurring (4-6 h) systemic hypertension and increased systemic vascular
resistance. WEB 2086 lessened the severity of TNF-alpha + IL-1
alpha-induced hemoconcentration and airway constriction, but did not modify
leukopenia, granulocytopenia, or the cytokine-induced increases in plasma
concentrations of thromboxane B2, prostaglandin F2 alpha, and
6-ketoprostaglandin F1 alpha. Microscopically, WEB 2086 did not modify the
increased number of granulocytes present in lung tissue derived from pigs
infused with TNF-alpha + IL-1 alpha. We conclude that PAF occupies a
physiological role in modulating TNF-alpha + IL-1 alpha-induced
hemoconcentration, the early changes in pulmonary hemodynamics, and the
later alterations in systemic hemodynamics.
