Fever evoked by macrophage inflammatory protein-1 (MIP-1) injected into preoptic or ventral septal area of rats depends on intermediary protein synthesis.
Macrophage inflammatory protein-1 (MIP-1), a novel cytokine composed of alpha/beta subunits, is released from macrophages during infection. MIP-1 injected intravenously in the rabbit or into the anterior hypothalamic, preoptic area (AH/POA) of the rat causes an intense fever, which is not blocked by prostaglandin synthesis inhibitors, ibuprofin or indomethacin, respectively. The purpose of this study was to determine the role of de novo protein synthesis on the fever evoked by MIP-1 applied to thermosensitive cells of the AH/POA. Guide cannulae were implanted bilaterally above the AH/POA or ventral septal area (VSA) and medially above the third cerebral ventricle in each of 11 male Sprague-Dawley rats. Following postoperative recovery, body temperature (Tb) was monitored by a colonic thermistor probe. The bilateral microinjection of MIP-1 in a dose of 14 pg per 0.5 microliters into the AH/POA caused a biphasic elevation in Tb to 0.9 +/- 0.2 degrees C within 1.0 h, which reached 1.5 +/- 0.2 degrees C within 3.0 h, and persisted for over 6.0 h. An identical injection of MIP-1 into the VSA increased Tb biphasically to 0.1 +/- 0.1 degrees C within 1.0 h and to 0.8 +/- 0.3 degrees C within 3.0 h. The infusion into the third ventricle of 80 micrograms/10 microliters of the inhibitor of protein synthesis, anisomycin, either 10 or 30 min before the microinjection of MIP-1 into the AH/POA, attenuated significantly the rise in Tb for 1.0 to 3.0 h or 2.5 to 3.0 h, respectively. These results coincide with the earlier finding that anisomycin inhibits both endotoxin- and IL-1 beta-induced fevers.(ABSTRACT TRUNCATED AT 250 WORDS)
Zawada
W M
WM
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock 72205.
Ruwe
W D
WD
Myers
R D
RD
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D054407:Chemokine CCL4; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced*; D007276:Injections, Intraventricular; D019402:Macrophage Inflammatory Proteins; D008297:Male; D008845:Microinjections; D015846:Monokines / Q000008:administration & dosage / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D009419:Nerve Tissue Proteins