Neuroendocrine regulation of autoimmune/inflammatory disease
Neuroendocrine regulation of autoimmune/inflammatory disease
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DOI：
10.1677/joe.0.1690429
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发表时间：
2001-06-01
影响因子：
4
通讯作者：
Sternberg, EM
中科院分区：
文献类型：
--
作者：
Sternberg, EM
免疫系统和神经系统之间的相互作用在调节宿主对炎性疾病的易感性和抵抗性中起重要作用。炎症和免疫反应以及疾病的神经内分泌调节发生在多个水平：系统性地，通过下丘脑-垂体-肾上腺轴刺激释放的糖皮质激素的抗炎作用;区域性地，通过免疫器官如胸腺内产生糖皮质激素和交感神经支配;局部地，在炎症部位。雌激素在免疫调节中也起重要作用，并导致在所有哺乳动物物种的雌性中观察到的自身免疫性/炎性疾病的发生率高约2至10倍。在炎症过程中，来自外周的细胞因子通过多种途径激活中枢神经系统。这导致刺激下丘脑-垂体-肾上腺轴，进而通过糖皮质激素的免疫抑制作用，通常抑制炎症。最近的研究表明，生理水平的糖皮质激素是免疫调节，而不仅仅是免疫抑制，导致细胞因子产生的模式从TH 1型模式转变为TH 2型模式。在任何水平和通过多种机制（无论是遗传的，还是通过手术或药物干预）中断该环可以使炎症抗性宿主对炎症疾病易感。该轴的过度激活，如在压力期间发生的，也可以通过糖皮质激素的免疫抑制作用影响感染性疾病的严重程度。这些相互作用已在许多动物模型中得到明确证明，跨越物种，菌株和疾病，并且也与人类炎症相关。自身免疫性和过敏性疾病，包括类风湿性关节炎、系统性红斑狼疮。虽然许多基因和环境因素有助于对自身免疫性炎性疾病的易感性和抵抗性，但是对神经肽、神经激素和神经递质在所有水平的组合的免疫应答的分子效应的充分理解已经开辟了新的治疗方法，并且对于基于这些原则的未来疗法的设计是必不可少的。
Interactions between the immune and nervous systems play an important role in modulating host susceptibility and resistance to inflammatory disease. Neuroendocrine regulation of inflammatory and immune responses and disease occurs at multiple levels: systematically, through the anti-inflammatory action of glucocorticoids released via hypothalamic-pituitary-adrenal axis stimulation; regionally, through production of glucocorticoids within and sympathetic innervation of immune organs such as the thymus; locally, at sites of inflammation. Estrogens also play an important role ill immune modulation, and contribute to the approximately 2- to 10-fold higher lncidence of autoimmune/inflammatory diseases seen in females of all mammalian species. During inflammation, cytokines from the periphery activate the central nervous system through multiple routes. This results in stimulation of the hypothalamic-pituitary-adrenal axis which. in turn through the immunosuppressive effects of the glucocorticoids, generally inhibits inflammation. Recent studies indicate that physiological levels of glucocorticoids are immunomodulatory rather than solely immunosuppressive, causing a shift in patterns of cytokine production from a TH1- to a TH2-type pattern. Interruption of this loop at any level and through multiple mechanisms, whether genetic, or through surgical or pharmacological interventions, can render an inflammatory resistant host susceptible to inflammation disease. Over-activation of this axis, as occurs during stress, can also affect severity of infectious disease through the immunosuppressive effects of the glucocorticoids. These interactions have been clearly demonstrated in many animal models, across species, strains and diseases, and are also relevant to human inflammatory. autoimmune and allergic illnesses, including rheumatoid arthritis, systemic lupus erythematosus. Sjorgen's syndrome, allergic asthma and atopic skin disease, While many genes and environmental factors contribute to susceptibility and resistance to autoimmune inflammatory diseases, a full understanding of the molecular effects on immune responses of combinations of neuropeptides, neurohormones and neurotransmitters at all levels has opened up new therapeutic approaches and are essential for the design of future therapies based on such principles.