Hematologic and immunomodulatory effects of an interleukin-1 receptor
antagonist coinfusion during low-dose endotoxemia in healthy humans
EV Granowitz, R Porat, JW Mier, SF Orencole, MV Callahan, JG Cannon, EA Lynch, K Ye, DD Poutsiaka and E Vannier
Department of Medicine, New England Medical Center Hospitals, Boston, MA
02111.
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.
Volume 82,
Issue 10,
pp. 2985-2990,
11/15/1993
Copyright © 1993 by The American Society of Hematology
