title: Immune-to-brain signaling and central prostaglandin E2 synthesis in fasted rats with altered lipopolysaccharide-induced fever.
abstract: 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 microg/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-1beta 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)-kappaB, suppressor of cytokine signaling (SOCS3), IL-1beta, 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.
authors.affiliation: Douglas Mental Health Univ. Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
authors.forename: Wataru
authors.initials: W
authors.lastname: Inoue
authors.forename: Gokce
authors.initials: G
authors.lastname: Somay
authors.forename: Stephen
authors.initials: S
authors.lastname: Poole
authors.forename: Giamal N
authors.initials: GN
authors.lastname: Luheshi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D005215:Fasting / Q000502:physiology; D005260:Female; D005334:Fever / Q000139:chemically induced*; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000502:physiology*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D000071876:Prostaglandin-E Synthases; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone