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Effects of recombinant soluble type I interleukin-1 receptor on human
inflammatory responses to endotoxin
HL Preas , D Reda, M Tropea, RW Vandivier, SM Banks, JM Agosti and AF Suffredini
Critical Care Medicine Department, Warren G. Magnuson Clinical Center,
National Institutes of Health, Bethesda, MD 20892-1662, USA.
Effects of soluble recombinant human type I interleukin-1 receptor (sIL-
1RI) were evaluated in 18 volunteers given intravenous endotoxin and
randomized to placebo (n = 6), low-dose (n = 6), or high-dose (n = 6)
sIL-1RI. Soluble IL-1RI decreased IL-1 beta (P = .001), but decreased
IL-1ra (P = .0001), and resulted in 10-fold and 43-fold dose-related
increases in sIL-1RI-IL-1ra complexes compared with placebo (P < or =
.001). High-dose sIL-1RI was associated with increased levels of
immunoactive tumor necrosis factor-alpha (P = .02), IL-8 (P = .0001), and
cell-associated IL-1 beta (P = .047). C-reactive protein levels were higher
after sIL-1RI than placebo (P = .035). Soluble IL-1RI decreased the
severity of chills (P = .03), but did not alter other symptoms, changes in
temperature, systemic hemodynamic responses, or changes in leukocyte and
platelet number. Thus, sIL-1RI had no discernable antiinflammatory effect
following endotoxin administration due in part to low levels of circulating
IL-1 beta and neutralization of IL-1ra inhibitory function. This latter
interaction represents an indirect mechanism of agonist activity elicited
by sIL-1RI and may contribute to increases in inflammatory mediators,
limiting therapy with sIL-1RI during endotoxemia.
Volume 88,
Issue 7,
pp. 2465-2472,
10/01/1996
Copyright © 1996 by The American Society of Hematology
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