Effects of histamine and α-fluoromethylhistidine on brain tumor necrosis factor levels in rats.

Besides the role of histamine (HA) as a neurotransmitter, a new concept has emerged presenting HA as an immunomodulator. Several studies have demonstrated interactions among HA, interleukin-1 β (IL-1 β) and tumor necrosis factor (TNF), suggesting a possible bidirectional communication among them. In this study we have investigated the effects of i.p. administrations of HA diphosphate (6 µmol/kg) and α-fluoromethylhistidine (FMH; 100 mg/kg) on TNF- α levels in the hippocampus, hypothalamus, and posterior hypothalamic region of the rat brain. The concentrations of TNF- α at 0 (Control, C) and 30 min after i.p. administration of HA were 0.26 ± 0.02 pg/mg and 0.32 ± 0.02 pg/mg in the hippocampus, 0.46 ± 0.04 pg/mg and 0.09 ± 0.006 pg/mg (p < 0.01) in the hypothalamus, and 0.47 ± 0.05 pg/mg and 0.26 ± 0.05 pg/mg in the posterior hypothalamic region. Three hours after FMH administration, an increase in the hippocampal levels of TNF- α was observed (0.43 ± 0.04 pg/mg; p < 0.01), while in the hypothalamus (0.11 ± 0.02 pg/mg; p < 0.01) and in the posterior hypothalamic region (0.21 ± 0.04 pg/mg; p < 0.05) a decrease in TNF- α levels was detected. These results suggest that changes in the histaminergic system influence TNF- α production in the brain in an area-specific fashion. [ABSTRACT FROM AUTHOR]