Brain IL-6-and PG-dependent actions of IL-1β and lipopolysaccharide in avian fever

Marais M, Maloney SK, Gray DA. Brain IL-6- and PG-dependent actions of IL-1 beta and lipopolysaccharide in avian fever. Am J Physiol Regul Integr Comp Physiol 301: R791-R800, 2011. First published June 15, 2011; doi:10.1152/ajpregu.00136.2011.-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-1 beta 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-1 beta 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-1 beta 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 PGE(2) was not upregulated in the cerebrospinal fluid of ducks made febrile with LPS. We conclude that IL-1 beta and IL-6 may well mediate fever by instigating an accelerated synthesis of brain-derived PG, of a class other than PGE(2), or that IL-6 serves as one of the terminal mediators of the avian febrile response.