Roles of brain cytokines in the adaptive responses to environmental stresses

我们研究了脑细胞因子在各种环境刺激应激反应中的作用，发现：（1）包括IL-1 β和IFN α在内的细胞因子不仅在炎症应激反应中表达，而且在非炎症应激反应中表达，如固定（1 MB）和热或冷暴露。(2)在大鼠视前内侧区（MPO）中，热暴露或冷暴露2小时诱导的Fos蛋白可使体温升高，因为c-fos mRNA反义寡核苷酸阻断Fos蛋白的表达可使热暴露（33 ℃）和冷暴露（4 ℃）时的体温降低。(3)化学刺激下丘脑外侧区（LHA）可抑制脾交感神经活动（SSNA），刺激下丘脑腹内侧核（VMH）可增强SSNA。此外，由于CRF拮抗剂α-螺旋CRF可阻断前列腺素E_2（PGE_2）诱导的SSNA激活，而CRF诱导的SSNA升高则不被阻断。 ...更多信息 在环氧化酶抑制剂水杨酸的作用下，CRF与PGE_2的作用呈序贯关系，PGE_2系统先激活，CRF再激活。(4)由于IMB诱导的小鼠脾NK细胞活性抑制可通过抗IL-1 β中和抗体预处理而减弱，因此脑IL-1 β在IMB诱导的免疫抑制中起重要作用。（5）肾上腺糖皮质激素抑制变应性接触性皮炎（ACD）的发展，ACD是T细胞依赖性迟发型超敏反应的原型，而它们在C-纤维存在下延迟ACD的终止。（6）肿瘤坏死因子-α（TNF-α）和IL-1 β分别抑制VMH和迷走神经背核的神经元活动，可能影响体温和胃酸分泌。（7）浴用IL-6抑制大鼠Schaffer侧支-CA通路的长时程增强。（8）谷氨酸可激活大鼠MPG神经元NMDA受体介导的Ca^<2+>依赖性K^+电流。（9）干细胞因子在小鼠苔藓纤维-CA 3通路中具有类似强直刺激的双脉冲易化作用。少

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