Febrile and metabolic tolerance to endotoxin and human recombinant interleukin-1 beta in rabbits.
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)
Yamashiro
O
O
Department of Physiology, Yamaguchi University School of Medicine, Japan.
Morimoto
A
A
Sakata
Y
Y
Watanabe
T
T
Murakami
N
N
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007501:Iron / Q000097:blood*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins; D015032:Zinc / Q000097:blood*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007501:Iron; D015032:Zinc