title: Interleukin (IL)-6 and IL-1 beta act synergistically within the brain to induce sickness behavior and fever in rats.
abstract: Pro-inflammatory cytokines interleukin (IL)-6 and IL-1 beta can act in the brain (centrally) to cause fever. Sickness behaviors which accompany fever also appear to involve the central action of IL-1 beta. We injected species-homologous rat IL-6 and IL-1 beta directly into the brains of conscious rats to examine the effect of these cytokines on fever, and two behaviors affected by sickness, voluntary wheel-running and food intake. Male Sprague-Dawley rats selected for their predisposition to spontaneously run on running wheels were used in the experiment. Each rat was anaesthetized and had a temperature-sensitive radiotransmitter implanted intra-abdominally, and a 23-gauge stainless steel guide cannula inserted stereotaxically over the lateral cerebral ventricle. Rats were randomly assigned to receive intracerebroventricular injections of three doses of either IL-1 beta or IL-6 (100 ng, 1 ng or 0.1 ng IL-1 beta and 200 ng, 20 ng or 2 ng IL-6), or one of three different combinations of IL-1 beta and IL-6. Rats receiving either IL-1 beta or IL-6 showed a dose-dependent increase in body temperature and decrease in wheel-running (ANOVA, p<0.0001). Only rats receiving the highest dose of IL-1 beta significantly decreased food intake and body mass compared to rats receiving vehicle (ANOVA, p<0.001). Doses of IL-1 beta and IL-6 which, when injected on their own were non-pyrogenic and did not affect food intake and body mass, induced fever and anorexia when they were co-injected centrally. These results show that species-homologous rat IL-6 and IL-1 beta can act directly within the brain to decrease voluntary activity and suggest they also can act synergistically to induce anorexia and fever.
authors.affiliation: Brain Function Research Group, School of Physiology, Medical School, University of the Witwatersrand, 7 York Road, Parktown, Gauteng, Johannesburg, South Africa. Lois.Harden@wits.ac.za
authors.forename: Lois M
authors.initials: LM
authors.lastname: Harden
authors.forename: Irné
authors.initials: I
authors.lastname: du Plessis
authors.forename: Stephen
authors.initials: S
authors.lastname: Poole
authors.forename: Helen P
authors.initials: HP
authors.lastname: Laburn
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects; D005334:Fever / Q000139:chemically induced*; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000633:toxicity*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012803:Sick Role
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6