Hypothalamic neuronal histamine modulates febrile response but not anorexia induced by lipopolysaccharide.
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.
Chiba
Seiichi
S
Department of Internal Medicine I, School of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Oita, 879-5593 Japan.
Itateyama
Emi
E
Oka
Kyoko
K
Masaki
Takayuki
T
Sakata
Toshiie
T
Yoshimatsu
Hironobu
H
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
D008070:Lipopolysaccharides; D006632:Histamine