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.
ARTICLES|
October 1, 1996
Effects of recombinant soluble type I interleukin-1 receptor on human inflammatory responses to endotoxin
HL 2nd Preas,
HL 2nd Preas
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892–1662, USA.
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D Reda,
D Reda
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892–1662, USA.
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M Tropea,
M Tropea
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892–1662, USA.
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RW Vandivier,
RW Vandivier
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892–1662, USA.
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SM Banks,
SM Banks
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892–1662, USA.
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JM Agosti,
JM Agosti
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892–1662, USA.
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AF Suffredini
AF Suffredini
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892–1662, USA.
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Blood (1996) 88 (7): 2465–2472.
Citation
HL 2nd Preas, D Reda, M Tropea, RW Vandivier, SM Banks, JM Agosti, AF Suffredini; Effects of recombinant soluble type I interleukin-1 receptor on human inflammatory responses to endotoxin. Blood 1996; 88 (7): 2465–2472. doi: https://doi.org/10.1182/blood.V88.7.2465.bloodjournal8872465
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