AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 1 39-L45, Copyright © 1994 by American Physiological Society
IL-1ra suppresses endotoxin-induced IL-1 beta and TNF-alpha release from mononuclear phagocytes
C. B. Marsh, S. A. Moore, H. A. Pope and M. D. Wewers
Division of Pulmonary and Critical Care Medicine, Ohio State University, Columbus 43210.
The proinflammatory effects of lipopolysaccharide (LPS) are modulated in
large part through the induction of interleukin-1 beta (IL-1 beta) and
tumor necrosis factor-alpha (TNF-alpha) release by mononuclear phagocytes.
However, IL-1's target cell effects can be suppressed by IL-1 receptor
agonist (IL-1ra). Because mononuclear phagocytes produce and respond to
IL-1 via IL-1 receptors, we hypothesized that IL-1ra may also be able to
block receptors on IL-1 producer cells and inhibit secondary IL-1-induced
IL-1 production. To test this hypothesis, mononuclear cells and alveolar
macrophages were stimulated with LPS in the presence of IL-1ra and analyzed
for IL-1 beta and TNF-alpha production. For mononuclear cells, IL-1ra
inhibited 6-h LPS- and IL-1 alpha-induced IL-1 beta release to 66 +/- 4% (P
= 0.001 by paired t test) and 39 +/- 7% (P = 0.0005 by paired t test) of
control, respectively. In addition, IL-1ra reduced both LPS- and IL-1
alpha-stimulated IL-1 beta mRNA levels to 78 and 37% of control,
respectively. Furthermore, IL-1ra downregulated both LPS and IL-1
alpha-induced TNF-alpha release to 84 +/- 4% (P = 0.012 by paired t test)
and 49 +/- 9% (P = 0.001 by paired t test) of control, respectively.
Alveolar macrophages demonstrated variable IL-1ra-induced suppression of
LPS-stimulated IL-1 beta and TNF-alpha release.(ABSTRACT TRUNCATED AT 250
WORDS)
