Increase of extracellular brain calcium involved in interleukin-1 beta-induced pyresis in the rabbit: antagonism by dexamethasone.

1. This study investigates the role of extracellular brain calcium in the hyperthermia induced by interleukin-1 beta (IL-1 beta). 2. Intracerebroventricular (i.c.v.) injection of IL-1 beta (12.5 ng kg-1) in rabbits caused a prompt and sustained rise in cerebrospinal fluid (CSF) Ca2+ concentration ([Ca2+]) followed by enhanced prostaglandin E2 (PGE2) release and hyperthermia. 3. A linear and significant correlation was observed between the increase in [Ca2+] induced by IL-1 beta and the rise in body temperature. 4. Ventriculo-cisternal perfusion with artificial CSF containing the calcium chelator EGTA (1.3 mM) blocked the IL-1-induced PGE2 release and countered the febrile response. 5. I.c.v. administration of dexamethasone (Dex) (2.4 and 24 micrograms kg-1) 100 min prior to IL-1 beta, dose-dependently antagonized the cytokine-induced Ca2+ increase, the PGE2 release and the febrile response. 6. These results suggest that changes in extracellular brain calcium are involved in the regulation of body temperature. In this light, the antipyretic action of Dex may be related to its effect on Ca2+ uptake.