AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 6 1180-R1185, Copyright © 1993 by American Physiological Society
Febrile and metabolic tolerance to endotoxin and human recombinant interleukin-1 beta in rabbits
O. Yamashiro, A. Morimoto, Y. Sakata, T. Watanabe and N. Murakami
Department of Physiology, Yamaguchi University School of Medicine, Japan.
We investigated whether or not tolerance of the febrile and metabolic
responses to human recombinant interleukin-1 beta (IL-1 beta) develops in
rabbits. Febrile tolerance to bacterial endotoxin was induced by daily
injections of lipopolysaccharide (LPS, 5.0 micrograms/kg iv). In
LPS-tolerant rabbits, the second phase of the biphasic fever induced by
intravenous injections of LPS (5.0 micrograms/kg) or IL-1 beta (2.0
micrograms/kg) was significantly reduced. However, the first phase was
almost the same as that observed in normal rabbits. Five daily injections
of IL-1 beta (2.0 micrograms/kg iv) resulted in the development of
tolerance of the febrile response to IL-1 beta. In IL-1 beta-tolerant
rabbits, the second peak of the biphasic fever was significantly reduced.
In addition, decreases in leukocyte count and plasma zinc induced by
intravenous injections of LPS or IL-1 beta were significantly reduced in
LPS- or IL-1 beta-tolerant rabbits. However the monophasic fever induced by
a smaller dose of IL-1 beta (0.5 microgram/kg iv) and the first peak of the
IL-1 biphasic fever were almost the same as those observed in normal
rabbits. Febrile responses induced in LPS- or IL-1 beta-tolerant rabbits by
intracerebroventricular injections of LPS (5.0 ng) or IL-1 beta (2.0 ng)
were similar to those observed in normal rabbits. The present results
suggest that tolerance of the febrile and metabolic responses to IL-1 beta
is developed after repeated injections of IL-1 beta and that reduced
responsiveness to IL-1 beta is partly involved in the development of LPS
tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
