Fever induced in rats by intrahypothalamic macrophage inflammatory protein (MIP)-1 beta: role of protein synthesis.
The effect of macrophage inflammatory protein-1 beta (MIP-1 beta) on body temperature, following its injection into the anterior hypothalamic pre-optic area (AH/POA), was examined by a radiotelemetry system in the freely moving rat. The purpose of this study was to examine the action of an inhibitor of protein synthesis, anisomycin, on the pyrexia which follows intrahypothalamic injection of MIP-1 beta. The micro-injection of 10 to 20 pg MIP-1 beta into the AH/POA induced a dose-dependent monophasic increase in body temperature, whereas a higher dose of 25 pg of the cytokine caused a biphasic febrile response. When MIP-1 beta was heated at 70 degrees C for 30 min prior to its administration, the pyrogenic response was abolished. Pretreatment of the micro-injection site in the AH/POA with 10 micrograms anisomycin did not alter the febrile response to 25 pg MIP-1 beta given at the same site in the AH/POA. When 10 mg/kg anisomycin was administered subcutaneously, the febrile response to 25 pg MIP-1 beta injected in the AH/POA was significantly suppressed. The present results suggest that fever caused by MIP-1 beta within the cells of the AH/POA may not require the synthesis of a new protein factor; however, the de novo synthesis of a protein outside of the AH/POA presumably plays a functional role, at least in part, in the intense fever produced by this cytokine in the hypothalamus.
Fernández-Alonso
A
A
Department of Pharmacology, Pediatrics and Radiology, Faculty of Medicine, University of Seville, Spain.
Miñano
F J
FJ
Myers
R D
RD
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D054407:Chemokine CCL4; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism*; D007032:Hypothalamus, Anterior / Q000378:metabolism / Q000502:physiology; D019402:Macrophage Inflammatory Proteins; D008297:Male; D008845:Microinjections; D015846:Monokines / Q000008:administration & dosage / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011301:Preoptic Area / Q000378:metabolism / Q000502:physiology; D011489:Protein Denaturation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D054407:Chemokine CCL4; D006131:Growth Inhibitors; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D000841:Anisomycin