 | MOLECULAR MECHANISMS OF FEVER
Copyright © 1998 by the New York Academy of Sciences
description
Annals of the New York Academy of Sciences 856:83-89 (1998)
© 1998 New York Academy of Sciences
Cytokines and Fever: Mechanisms and Sites of Action
GIAMAL N. LUHESHIa
School of Biological Sciences, University of Manchester, Manchester, UK
aAddress for correspondence: School of Biological Sciences, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK. Phone, (44) 161 275 5604; fax, (44) 161 275 5948; e-mail, Gluheshi{at}man.ac.uk
The cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-  induce increases in body temperature via direct and indirect actions on the brain and are believed to act as endogenous pyrogens. We studied the mechanisms of action of these cytokines on fever in rats. Local administration of lipopolysaccharide (LPS) into a subcutaneous air pouch elicits marked fever, accompanied by increases in the levels of TNF- , IL-1, and IL-6 in the pouch, but only IL-6 in the plasma. Thus, TNF- and IL-1 probably act locally to stimulate the release of a secondary circulating mediator(s) (e.g., IL-6) that can interact with the brain. Neural afferents have also been implicated in relaying messages to the brain. Pyrogenic responses are reportedly attenuated by subdiaphragmatic vagotomy; however, we failed to observe inhibition of fever in vagotomized rats injected with either LPS or a pyrogenic dose of IL-1, although behavioral responses are abolished.
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