title: Hypothalamic neuronal histamine modulates febrile response but not anorexia induced by lipopolysaccharide.
abstract: This study examined the contribution of hypothalamic neuronal histamine (HA) to the anorectic and febrile responses induced by lipopolysaccharide (LPS), an exogenous pyrogen, and the endogenous pyrogens interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Intraperitoneal (ip) injection of LPS, IL-1beta, or TNF-alpha suppressed 24-hr cumulative food intake and increased rectal temperature in rats. To analyze the histaminergic contribution, rats were pretreated with intracerebroventricular (icv) injection of 2.44 mmol/kg or ip injection of 244 mmol/kg of alpha-fluoromethylhistidine (FMH), a suicide inhibitor of histidine decarboxylase (HDC), to deplete neural HA. The depletion of neural HA augmented the febrile response to ip injection of LPS and IL-1beta and alleviated the anorectic response to ip injection of IL-1beta. However, the depletion of neural HA did not modify the LPS-induced anorectic response or TNF-alpha-induced febrile and anorectic responses. Consistent with these results, the rate of hypothalamic HA turnover, assessed by the accumulation of tele-methylhistamine (t-MH), was elevated with ip injections of LPS and IL-1beta, but unaffected by TNF-alpha at equivalent doses. This suggests that (i) LPS and IL-1beta activate hypothalamic neural HA turnover; (ii) hypothalamic neural HA suppresses the LPS- and IL-1beta-induced febrile responses and accelerates the IL-1beta-induced anorectic response; and (iii) TNF-alpha modulates the febrile and anorectic responses via a neural HA-independent pathway. Therefore, hypothalamic neural HA is involved in the IL-1beta-dominant pathway, rather than the TNF-alpha-dominant pathway, preceding the systemic inflammatory response induced by exogenous pyrogens, such as LPS. Further research on this is needed.
authors.affiliation: Department of Internal Medicine I, School of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Oita, 879-5593 Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Emi
authors.initials: E
authors.lastname: Itateyama
authors.forename: Kyoko
authors.initials: K
authors.lastname: Oka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Masaki
authors.forename: Toshiie
authors.initials: T
authors.lastname: Sakata
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D005334:Fever / Q000503:physiopathology*; D006632:Histamine / Q000502:physiology*; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008070:Lipopolysaccharides; D006632:Histamine