Roles of brain cytokines in the adaptive responses to environmental stresses

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We have investigated the roles of brain cyotokines in the stress responses to various environmental stimuli, and found that ;(1) Cytokines including IL-1beta and IFNalpha were expressed in the brain in response to not only inflammatory stresses but also non-inflammatory stresses such as immobilization (1MB) and heat or cold exposure.(2) Fos protein induced in rat medial preoptic area (MPO) in response to heat or cold exposure for 2 hours works to elevate body temperature since blockade of Fos expression by antisenseoligo DNA for c-fos mRNA results in the decrease in body temperature both in heat (33ﾟC) and cold (4ﾟC) exposure.(3) Splenic sympathetic nerve activity (SSNA) was suppressed by chemical stimulation of the lateral hypothalamic area (LHA) and enhanced by that of the ventromedial hypothalamic nucleus (VMH). In addition, since the prostaglandin E2 (PGE2)-induced activation of SSNA was blocked by a CRF antagonist, a-helical CRF, while the CRF-induce elevation of SSNA was not bloc … More ked by a cyclooxygenase inhibitor, salicylate, it is suggested that there is a sequential relationship between actions of CRF and PGE2, with an activation of PGE2 system followed by that of CRF in the brain.(4) Since the IMB-induced suppression of splenic NK cell activity in mice was attenuated by pretreatment with anti-IL-1beta neutralizing antibody, brain IL-1beta plays a significant role in the IMB-induced immunosuppression.(5)Adrenal glucocorticoids suppress the development of allergic contact dermatits (ACD), a prototype of T cell-dependent delayed type hypersensitivity, while they delay the termination of ACD in the presence of C-fibers.(6)Tumor necrosis factor-alpha (TNF-alpha) and IL-1beta suppress the neuronal activity in the VMH, and dorsal mortor nucleus of the vagus, respectively, probably affecting body temperature and gastric acid secretion.(7)Bath application of IL-6 resulted in a suppression of long-term potentiation in rat Schaffer collateral-CA pathway.(8)Glutamate induced an activation of NMDA receptor-mediated Ca^<2+>-dependent K^+ current in rat MPG neurons.(9)Stem cell factor modulated a paired-pulse facilitation like tetanic stimulation in mouse mossy fiber-CA3 pathway. Less