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Interleukin-1 receptor antagonist circulates in experimental inflammation
and in human disease
E Fischer, KJ Van Zee, MA Marano, CS Rock, JS Kenney, DD Poutsiaka, CA Dinarello, SF Lowry and LL Moldawer
Department of Surgery, Cornell University Medical College, New York, NY
10021.
Interleukin-1 receptor antagonist (IL-1ra) is a 22-Kd protein that shares
homology with IL-1 beta, binds to the IL-1 receptor, but has no known
agonist properties. This inhibitor appears to be the first cytokine whose
sole function is to block the actions of another cytokine. Exogenous IL-1ra
administration has been shown to reduce mortality in experimental septic
shock. We now report that IL-1ra is endogenously produced and circulates in
experimental inflammation and in clinical disease. After experimental
endotoxemia in human volunteers, IL-1ra concentrations increase from a
baseline concentration of 460 +/- 200 pg mL-1 to 14,870 +/- 290 pg mL-1 at
3 hours (P less than .05). IL-1ra is also detectable in all plasma samples
from critically ill patients with a mean concentration of 8,680 +/- 2,060
pg mL-1 (range 320 to 55,370 pgs mL-1). In nonhuman primates, Escherichia
coli septic shock induces elevated plasma levels of IL-4ra (P less than
.05). However, in animals that eventually succumb to septic shock, Il-1ra
appears in quantities presumed inadequate to block the pathologic sequelae
associated with high IL-1 beta levels. The findings suggest that IL-1ra may
play a role in modulating the systemic host responses to a variety of
nonlethal disease states by altering the balance between cytokines and
their antagonists.
Volume 79,
Issue 9,
pp. 2196-2200,
05/01/1992
Copyright © 1992 by The American Society of Hematology
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