Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans

E. V. Granowitz, R. Porat, J. W. Mier, S. F. Orencole, M. V. Callahan, Joseph Gerard Cannon, E. A. Lynch, K. Ye, D. D. Poutsiaka, E. Vannier, L. Shapiro, J. P. Pribble, D. M. Stiles, M. A. Catalano, S. M. Wolff, C. A. Dinarello

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin- induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra.

Original languageEnglish (US)
Pages (from-to)2985-2990
Number of pages6
JournalBlood
Volume82
Issue number10
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Granowitz, E. V., Porat, R., Mier, J. W., Orencole, S. F., Callahan, M. V., Cannon, J. G., Lynch, E. A., Ye, K., Poutsiaka, D. D., Vannier, E., Shapiro, L., Pribble, J. P., Stiles, D. M., Catalano, M. A., Wolff, S. M., & Dinarello, C. A. (1993). Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans. Blood, 82(10), 2985-2990.