EFFECTS OF HISTAMINE AND ALPHA-FLUOROMETHYLHISTIDINE ON BRAIN-TUMOR NECROSIS FACTOR LEVELS IN RATS

Besides the role of histamine (HA) as a neurotransmitter, a new concep t has emerged presenting HA as an immunomodulator. Several studies hav e demonstrated interactions among HA, interleukin-1 beta (IL-1 beta) a nd tumor necrosis factor (TNF), suggesting a possible bidirectional co mmunication among them. In this study we have investigated the effects of i.p. administrations of HA diphosphate (6 mu mol/kg) and alpha-flu oromethylhistidine (FMH; 100 mg/kg) on TNF-alpha levels in the hippoca mpus, hypothalamus, and posterior hypothalamic region of the rat brain . The concentrations of TNF-alpha 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 a dministration, an increase in the hippocampal levels of TNF-alpha 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-alpha levels was de tected. These results suggest that changes in the histaminergic system influence TNF-alpha production in the brain in an area-specific fashi on.