AJP - Regulatory, Integrative and Comparative Physiology, Vol 259, Issue 5 993-R997, Copyright © 1990 by American Physiological Society
Induction of plasma inhibitors of interleukin 1 and TNF-alpha activity by endotoxin administration to normal humans
G. A. Spinas, D. Bloesch, M. T. Kaufmann, U. Keller and J. M. Dayer
Department of Internal Medicine and Research, University Hospital, Basel, Switzerland.
Several naturally occurring inhibitors of interleukin 1 (IL-1) and tumor
necrosis factor-alpha (TNF-alpha) have been demonstrated both in serum and
urine of febrile patients. These factors are considered to be part of a
regulatory system counteracting potential deleterious effects of the
cytokines. We have assayed plasma samples of volunteers who received a
bolus intravenous injection of either 4 ng/kg body wt of Escherichia coli
endotoxin (n = 6) or 0.9% saline (n = 4) for the presence of IL-1 and
TNF-alpha inhibitory activity. Plasma obtained 3 h after endotoxin
injection inhibited IL-1-induced PGE2 release from fibroblasts by 57% (P
less than 0.001 vs. baseline and saline controls, respectively). Maximal
IL-1 inhibitory capacity coincided with fever and tended to disappear with
declining body temperature. Normal plasma was found to inhibit
TNF-alpha-induced PGE2 release by 20-35%. This inhibitory effect increased
to 50-60% in plasma obtained during endotoxinemia. Maximal TNF-alpha
inhibitory capacity became detectable when circulating TNF-alpha levels
peaked at 120 min after the injection of endotoxin. Our data demonstrate
that both IL-1 and TNF-alpha inhibitory activity can be induced
experimentally by intravenous endotoxin administration to humans and that
their appearance coincides with fever and circulating TNF-alpha levels.
