Berczi I, Chalmers I M, Nagy E, Warrington R J
Department of Immunology, University of Manitoba, Winnipeg, Canada.
Baillieres Clin Rheumatol. 1996 May;10(2):227-57. doi: 10.1016/s0950-3579(96)80016-1.
Current evidence indicates that the neuroendocrine system is the highest regulator of immune/inflammatory reactions. Prolactin and growth hormone stimulate the production of leukocytes, including lymphocytes, and maintain immunocompetence. The hypothalamus-pituitary-adrenal axis constitutes the most powerful circuit regulating the immune system. The neuropeptides constituting this axis, namely corticotrophin releasing factor, adrenocorticotrophic hormone, alpha-melanocyte stimulating hormone, and beta-endorphin are powerful immunoregulators, which have a direct regulatory effect on lymphoid cells, regulating immune reactions by the stimulation of immunoregulatory hormones (glucocorticoids) and also by acting on the central nervous system which in turn generates immunoregulatory nerve impulses. Peptidergic nerves are major regulators of the inflammatory response. Substance P and calcitonin gene-related peptide are pro-inflammatory mediators and somatostatin is anti-inflammatory. The neuroendocrine regulation of the inflammatory response is of major significance from the point of view of immune homeostasis. Malfunction of this circuit leads to disease and often is life-threatening. The immune system emits signals towards the neuroendocrine system by cytokine mediators which reach significant blood levels (cytokine-hormones) during systemic immune/inflammatory reactions. Interleukin-1, -6, and TNF-alpha are the major cytokine hormones mediating the acute phase response. These cytokines induce profound neuroendocrine and metabolic changes by interacting with the central nervous system and with many other organs and tissues in the body. Corticotrophin releasing factor functions under these conditions as a major co-ordinator of the response and is responsible for activating the ACTH-adrenal axis for regulating fever and for other CNS effects leading to a sympathetic outflow. Increased ACTH secretion leads to glucocorticoid production. alpha-melanocyte stimulating hormone functions under these conditions as a cytokine antagonist and an anti-pyretic hormone. The sympathetic outflow, in conjunction with increased adrenal activity. leads to the elevation of catecholamines in the bloodstream and in tissues. Current evidence suggests that neuroimmune mechanisms are essential in normal physiology, such as tissue turnover, involution, atrophy, intestinal function, and reproduction. Host defence against infection, trauma and shock relies heavily on the neuroimmunoregulatory network. Moreover, abnormalities of neuroimmunoregulation contribute to the aetiology of autoimmune disease, chronic inflammatory disease, immunodeficiency, allergy, and asthma. Finally, neuroimmune mechanisms play an important role in regeneration and healing.
目前的证据表明，神经内分泌系统是免疫/炎症反应的最高调节者。催乳素和生长激素刺激包括淋巴细胞在内的白细胞生成，并维持免疫能力。下丘脑-垂体-肾上腺轴构成调节免疫系统的最强大回路。构成该轴的神经肽，即促肾上腺皮质激素释放因子、促肾上腺皮质激素、α-黑素细胞刺激素和β-内啡肽，是强大的免疫调节因子，它们对淋巴细胞有直接调节作用，通过刺激免疫调节激素（糖皮质激素）以及作用于中枢神经系统来调节免疫反应，而中枢神经系统反过来又产生免疫调节神经冲动。肽能神经是炎症反应的主要调节者。P物质和降钙素基因相关肽是促炎介质，而生长抑素是抗炎介质。从免疫稳态的角度来看，炎症反应的神经内分泌调节具有重要意义。该回路功能失调会导致疾病，且常常危及生命。免疫系统通过细胞因子介质向神经内分泌系统发出信号，在全身性免疫/炎症反应期间，这些细胞因子会达到显著的血液水平（细胞因子-激素）。白细胞介素-1、-6和肿瘤坏死因子-α是介导急性期反应的主要细胞因子激素。这些细胞因子通过与中枢神经系统以及体内许多其他器官和组织相互作用，诱导深刻的神经内分泌和代谢变化。在这些情况下，促肾上腺皮质激素释放因子作为反应的主要协调者发挥作用，并负责激活促肾上腺皮质激素-肾上腺轴以调节发热以及导致交感神经输出的其他中枢神经系统效应。促肾上腺皮质激素分泌增加会导致糖皮质激素生成。在这些情况下，α-黑素细胞刺激素作为细胞因子拮抗剂和退热激素发挥作用。交感神经输出与肾上腺活动增加一起，导致血液和组织中儿茶酚胺水平升高。目前的证据表明，神经免疫机制在正常生理过程中至关重要，如组织更新、退化、萎缩、肠道功能和生殖。宿主对感染、创伤和休克的防御严重依赖神经免疫调节网络。此外，神经免疫调节异常促成自身免疫性疾病、慢性炎症性疾病、免疫缺陷、过敏和哮喘的病因。最后，神经免疫机制在再生和愈合中起重要作用。
