Abstract
This study examined the contribution of hypothalamic neuronal histamine (HA) to the anorectic and febrlle responses induced by lipopolysaccharide (LPS), an exogenous pyrogen, and the endogenous pyrogens interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Intraperitoneal (ip) Injection of LPS, IL-1β, or TNF-α suppressed 24-hr cumulative food intake and increased rectal temperature in rats.
To analyze the histamlnergic contribution, rats were pre-treated with intracerebroventricular (icv) injection of 2.44 mmol/ kg or ip injection of 244 mmol/kg of α-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-lnduced anorectic response or TNF-α-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-α 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-1β-induced febrile responses and accelerates the IL-1ß-induced anorectic response; and (iii) TNF-α 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-α-dominant pathway, preceding the systemic Inflammatory response induced by exogenous pyrogens, such as LPS. Further research on this is needed.