AJP - Regulatory, Integrative and Comparative Physiology, Vol 259, Issue 1 126-R132, Copyright © 1990 by American Physiological Society

ARTICLES

Plasma profiles of IL-6 and TNF with fever-inducing doses of lipopolysaccharide in dogs

D. R. LeMay, L. G. LeMay, M. J. Kluger and L. G. D'Alecy
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.

This study was designed to test the tumor necrosis factor (TNF) WEHI 164 clone 13 bioassay and the interleukin 6 (IL-6) B9 bioassay for sensitivity to endogenously produced dog TNF and IL-6 and then to use these assays to examine the associations between these cytokines and lipopolysaccharide (LPS)-induced fever. When dogs were injected with LPS (40, 10, 1, 0.1, and 0.01 microgram/kg), the resulting fever was dose dependent. A plot of plasma cytokine changes over time following LPS injections showed that the plasma TNF-like activity appeared to increase in an all-or-none dose response, whereas the increase in plasma IL-6-like activity appeared to be log dose dependent. Plasma TNF-like and IL-6-like activity were then separately plotted against temperature change (fever). Statistical analysis supported the interpretation that both TNF-like and IL-6-like activity were related to LPS-fever in an all-or-none manner, with IL-6 having a threshold region. We conclude that if these cytokines are circulating mediators of fever, they may induce fever in an all-or-none fashion.

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