HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chiba, S. Articles by Yoshimatsu, H. Search for Related Content PubMed PubMed Citation Articles by Chiba, S. Articles by Yoshimatsu, H.

---

ORIGINAL RESEARCH ARTICLE

Hypothalamic Neuronal Histamine Modulates Febrile Response but Not Anorexia Induced by Lipopolysaccharide

Seiichi Chiba^*, Emi Itateyama^*, Kyoko Oka, Takayuki Masaki^*, Toshiie Sakata and Hironobu Yoshimatsu^*,1

^* Department of Internal Medicine I, School of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Oita, 879-5593; Department of Pediatric Dentistry, Faculty of Dentistry, Kyushu University, Maidashi, Fukuoka, 814-00; and Graduate School of Health and Nutritional Sciences, Faculty of Nutritional Sciences, Nakamura Gakuen University, Befu, Fukuoka, 814-0198, Japan

To whom requests for reprints should be addressed at ¹ Department of Internal Medicine I, School of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Oita, 879-5593 Japan. E-mail: hiroy{at}med.oita-u.ac.jp

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-1ß (IL-1ß) and tumor necrosis factor- (TNF-). Intraperitoneal (ip) injection of LPS, IL-1ß, or TNF- 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 -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-1ß and alleviated the anorectic response to ip injection of IL-1ß. However, the depletion of neural HA did not modify the LPS-induced anorectic response or TNF-–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-1ß, but unaffected by TNF- at equivalent doses. This suggests that (i) LPS and IL-1ß activate hypothalamic neural HA turnover; (ii) hypothalamic neural HA suppresses the LPS- and IL-1ß–induced febrile responses and accelerates the IL-1ß–induced anorectic response; and (iii) TNF- modulates the febrile and anorectic responses via a neural HA-independent pathway. Therefore, hypothalamic neural HA is involved in the IL-1ß–dominant pathway, rather than the TNF-–dominant pathway, preceding the systemic inflammatory response induced by exogenous pyrogens, such as LPS. Further research on this is needed.

Key Words: hypothalamic neuronal histamine • LPS • TNF- • anorexia • thermogenesis

This article has been cited by other articles:

				H. L. Haas, O. A. Sergeeva, and O. Selbach Histamine in the Nervous System Physiol Rev, July 1, 2008; 88(3): 1183 - 1241. [Abstract] [Full Text] [PDF]