Macrophage inflammatory protein-1beta induces dexamethasone-unresponsive fever in rats.
It has been hypothesized that endogenous glucocorticoids represent an important negative feedback system involved in the modulation of cytokine-induced fever through the inhibition of prostaglandins (PG) production in the preoptic anterior hypothalamus (AH/POA). The purpose of this study was to determinate whether glucocorticoids modulate the PG-independent febrile response induced by macrophage inflammatory protein-1beta (MIP-1beta) in a manner similar to other pyrogenic cytokines. Subcutaneous pretreatment with dexamethasone (1, 2 and 4 mg/kg; 1 h) had no effect on fever induced by microinjection of 50 pg MIP-1beta into the rat's AH/POA. It is demonstrated for the first time that, unlike other cytokines, fever induced by MIP-1beta is independent of glucocorticoid modulation. Finally, these results offer new perspectives about the pathogenesis of glucocorticoid-unresponsive pyrexia.
Research Unit, University Hospital of Valme, Seville, Spain.
E
E
Tavares
F J
FJ
Minano
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D054407:Chemokine CCL4; D003907:Dexamethasone / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced* / Q000188:drug therapy; D019402:Macrophage Inflammatory Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D011301:Preoptic Area; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D003907:Dexamethasone