Effects of neurotoxic lesions in histaminergic neurons on brain tumor necrosis factor levels.

Histamine (HA) is a biogenic amine involved in the regulation of neurovegetative, cognitive, neuroendocrine and neuroimmune functions in the central nervous system (CNS). A bidirectional interaction between the CNS and the neuroimmune system has been demonstrated in recent years. However, data concerning brain HA-cytokine interactions are scarce. In this study we have evaluated tumor necrosis factor-alpha (TNF-alpha) levels in the posterior hypothalamic region (PHR) and hippocampus (HP) of rats with: (a) bilateral ibotenic acid neurotoxic lesions in histaminergic neurons located in the PHR (I); (b) saline injections in the PHR (S); and (c) sham operation (C), two weeks after neurosurgery. The bilateral disruption of PHR HA neurons with ibotenic acid decreased TNF-alpha levels in the PHR with respect to sham-operated (C), but not saline-injected (S), rats. In contrast, hippocampal TNF-alpha concentrations were higher in lesioned rats (I) than in C and S animals. Our results indicate that the neurotoxic destruction of HA neurons decreases TNF-alpha synthesis in the hypothalamus while enhancing TNF-alpha production in the hippocampus, suggesting that neuronal HA might be involved in the regulation of the brain TNF-alpha system.