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Multiple mechanisms mediate antipyretic action of glucocorticoids. 1995

M M Coelho, and G Luheshi, and S J Hopkins, and I R Pelá, and N J Rothwell
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.

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 and 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 compared with sham-operated animals and exhibited a lower plasma-to-CSF IL-6 ratio than sham-operated animals. Dexamethasone pretreatment also inhibited 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.

UI MeSH Term Description Entries
D008297 Male Males
D011453 Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Prostaglandin,Prostanoid,Prostanoids
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004731 Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Endotoxin
D005334 Fever An abnormal elevation of body temperature, usually as a result of a pathologic process. Pyrexia,Fevers,Pyrexias
D005938 Glucocorticoids A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D000315 Adrenalectomy Excision of one or both adrenal glands. (From Dorland, 28th ed) Adrenalectomies
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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