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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/R133    most recent 90335.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Inoue, W. Articles by Luheshi, G. N. PubMed PubMed Citation Articles by Inoue, W. Articles by Luheshi, G. N.

INFLAMMATION CYTOKINES, NEUROIMMUNE INTERACTIONS

Immune-to-brain signaling and central prostaglandin E₂ synthesis in fasted rats with altered lipopolysaccharide-induced fever

¹Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada; and ²Department of Endocrinology, National Institute for Biological Standards and Control, Potters Bar, United Kingdom

Submitted 1 April 2008 ; accepted in final form 9 May 2008

Acute starvation attenuates the fever response to pathogens in several mammalian species. The underlying mechanisms responsible for this effect are not fully understood but may involve a compromised immune and/or thermoregulatory function, both of which are prerequisites for fever generation. In the present study, we addressed whether the impaired innate immune response contributes to the reported attenuation of the fever response in fasted rats during LPS-induced inflammation. Animals fasted for 48 h exhibited a significant and progressive hypothermia prior to drug treatment. An intraperitoneal injection of LPS (100 µg/kg) resulted in a significantly attenuated fever in the fasted animals compared with the fed counterparts. This attenuation was accompanied by the diminution in the concentration of some [TNF and IL-1 receptor antagonist (RA)] but not all (IL-1β and IL-6) of the plasma cytokines normally elevated in association with the fever response. Nevertheless, fasting had no effect on the LPS-induced inflammatory responses at the level of the brain, as assessed by mRNA expressions of inhibitory factor(I)-B, suppressor of cytokine signaling (SOCS3), IL-1β, cyclooxygenase (COX)-2, and microsomal PGE synthase (mPGES)-1 in the hypothalamus, as well as by PGE₂ elevations in the cerebrospinal fluid. In contrast, fasting significantly attenuated the fever response to central PGE₂ injection. These results show that fasting does not alter the febrigenic signaling from the periphery to the brain important for central PGE₂ synthesis but does affect thermoregulatory mechanisms downstream of and/or independent of central PGE₂ action.

thermoregulation; acute starvation; cyclooxygenase; hypothermia