The effects of the protein synthesis inhibitor anisomycin on the febrile responses to intracerebroventricular injections of bacterial pyrogen, arachidonic acid and prostaglandin E2.
1. Anisomycin (15 mg/kg) was administered s.c. to cats at ambient temperatures of 5 degrees C, 20 degrees C and 38 degrees C. It produced biphasic effects on body temperature at 5 degrees C and 20 degrees C, an initial fall in temperature followed by a rise in body temperature, and a rise in body temperature of long latency at 38 degrees C. 2. Anisomycin (15 mg/kg) attenuated the hyperthermic responses to centrally injected PGE2 (1 microgram) at all ambient temperatures studied and also completely abolished the hyperthermic response to arachidonic acid (100 ng i.c.v.) at 20 degrees C. 3. Shigella dysenteriae (100 ng i.c.v.) raised the body temperature of cats by increasing heat production and reducing heat loss at 5 degrees C and 20 degrees C, and by increasing heat conservation at 38 degrees C. Anisomycin (15 mg/kg s.c.) pretreatment did not affect the temperature responses to the pyrogen at 20 degrees C and 38 degrees C, but did reduce the responses to Shigella dysenteriae (100 ng and 1 microgram i.c.v.) at 5 degrees C. 4. Anisomycin (15 mg/kg s.c.) was administered to cats, 90 min after the injection of Shigella dysenteriae (100 ng i.c.v.), at 20 degrees C at the onset of hyperthermia in control experiments. Under these conditions, no hyperthermia was observed over a 2 h period following anisomycin injection. 5. It is concluded that anisomycin interferes with pyrogen induced fever by acting at a site after PGE2 in the pathway to fever.
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001833:Body Temperature Regulation / Q000187:drug effects; D002415:Cats; D015232:Dinoprostone; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D007276:Injections, Intraventricular; D019081:O Antigens; D011458:Prostaglandins E / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011749:Pyrogens / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D012762:Shigella dysenteriae / Q000276:immunology
D000942:Antigens, Bacterial; D001095:Arachidonic Acids; D019081:O Antigens; D011458:Prostaglandins E; D011500:Protein Synthesis Inhibitors; D011749:Pyrogens; D011759:Pyrrolidines; D016718:Arachidonic Acid; D000841:Anisomycin; D015232:Dinoprostone