Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease.
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.
Fischer
E
E
Department of Surgery, Cornell University Medical College, New York, NY 10021.
Van Zee
K J
KJ
Marano
M A
MA
Rock
C S
CS
Kenney
J S
JS
Poutsiaka
D D
DD
Dinarello
C A
CA
Lowry
S F
SF
Moldawer
L L
LL
D000328:Adult; D000818:Animals; D004731:Endotoxins / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D010215:Papio; D011506:Proteins / Q000032:analysis*; D012772:Shock, Septic / Q000097:blood; D012795:Sialoglycoproteins
D004731:Endotoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D011506:Proteins; D012795:Sialoglycoproteins