title: Brain IL-6- and PG-dependent actions of IL-1β and lipopolysaccharide in avian fever.
abstract: There is no persuasive evidence of a correlation between proinflammatory cytokines and avian fever. In this study, for the first time, we use avian cytokines to investigate a role for proinflammatory cytokines in the central component of avian fever. IL-1β and IL-6 injected intracerebroventricularly into Pekin ducks (n = 8) initiated robust fevers of equal magnitude and duration, although there was a significant difference in the latency to a febrile response. In addition, the IL-1β-induced fever could be abolished with an intracerebroventricular injection of antibodies to avian IL-6 or an oral administration of a PG synthesis inhibitor. Our findings indicate the following sequence of events within the central component of the avian febrile mechanism: IL-1β gives rise to bioactive IL-6, which stimulates an accelerated synthesis of PGs, and these PGs then adjust the sensitivity of warm-sensitive neurons in the avian brain stem to mediate fever. Yet PGE₂ was not upregulated in the cerebrospinal fluid of ducks made febrile with LPS. We conclude that IL-1β and IL-6 may well mediate fever by instigating an accelerated synthesis of brain-derived PG, of a class other than PGE₂, or that IL-6 serves as one of the terminal mediators of the avian febrile response.
authors.affiliation: School of Physiology, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa. manette.marais@wits.ac.za
authors.forename: Manette
authors.initials: M
authors.lastname: Marais
authors.forename: Shane K
authors.initials: SK
authors.lastname: Maloney
authors.forename: David A
authors.initials: DA
authors.lastname: Gray
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001833:Body Temperature Regulation / Q000187:drug effects; D001921:Brain / Q000276:immunology* / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D004008:Diclofenac / Q000008:administration & dosage; D015232:Dinoprostone / Q000378:metabolism; D004372:Ducks; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology / Q000662:veterinary*; D018836:Inflammation Mediators / Q000378:metabolism*; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000378:metabolism; D015850:Interleukin-6 / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D011201:Poultry Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011930:Reaction Time; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D000906:Antibodies; D016861:Cyclooxygenase Inhibitors; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011453:Prostaglandins; D011994:Recombinant Proteins; C440499:lipopolysaccharide, Escherichia coli O111 B4; D004008:Diclofenac; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone