Multiple mechanisms mediate the antipyretic action of
glucocorticoids.
Coelho, M. M., Luheshi, G., Hopkins, S. J., Pel, I. R., Rothwell, N.
J.
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of
Ribeiro Preto, University of So Paulo, Ribeiro Preto, SP, Brazil,
Rheumatic Diseases Centre, Clinical Sciences Building, Hope Hospital,
University of Manchester, School of Biological Sciences, University
of Manchester, 1.124, Stopford Building, Oxford Road, Manchester M13
9PT, UK
APStracts 2:0078R, 1995.
Glucocorticoids inhibit various components of the acute phase response
particularly the increase in body temperature (fever) induced by a
variety of stimuli. In the present study these observations have been
extended and we have determined the effect of glucocorticoid
treatment or surgical adrenalectomy on the cytokine and prostaglandin
(PG) concentrations in plasma and cerebrospinal fluid (CSF) during
the febrile response to endotoxin. Dexamethasone treatment, either
before or after endotoxin injection, markedly inhibited fever, the
increased plasma interleukin (IL)-6 and CSF IL-6, PGE2 and
PGF2[alpha] concentrations. Adrenalectomized (ADX) rats showed higher
fevers and plasma and CSF IL-6, PGE2 and PGF2[alpha], concentrations
when compared to sham-operated animals and exhibited a lower
plasma/CSF IL-6 ratio than sham-operated animals. Dexamethasone pre
-treatment also inhibited the fever induced by centrally-injected
TNF[alpha], IL-1[beta] or IL-6. Pyrogenic response to IL-8 was not
modified by indomethacin, but was markedly inhibited by prior
treatment with dexamethasone. These results support the hypothesis
that endogenous glucocorticoids function as part of an inhibitory
feedback system involved in the modulation of fever, and that
multiple mechanisms may be involved in their antipyretic effect.
Received 29 September 1994; accepted in final form 17 March 1995.
APS Manuscript Number R564-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 April 1995.