Elenkov Ilia J, Iezzoni Domenic G, Daly Adrian, Harris Alan G, Chrousos George P
Division of Rheumatology, Immunology and Allergy, Georgetown University Medical Center, Washington, D.C., USA.
Neuroimmunomodulation. 2005;12(5):255-69. doi: 10.1159/000087104.
Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1 versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic 'overshooting' with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.
细胞因子介导并控制免疫和炎症反应。在维持体内平衡、健康和幸福方面，细胞因子、炎症与适应性反应之间存在复杂的相互作用。与应激反应一样，炎症反应对生存至关重要，并且应根据刺激因素和时间进行调整。全面的全身性炎症反应会刺激四个主要程序：急性期反应、疾病综合征、疼痛程序和应激反应，这些反应由下丘脑 - 垂体 - 肾上腺轴和交感神经系统介导。常见的人类疾病，如特应性/过敏、自身免疫、慢性感染和败血症，其特征在于促炎与抗炎以及辅助性T细胞（Th）1与Th2细胞因子平衡失调。最近的证据还表明，促炎细胞因子参与动脉粥样硬化和重度抑郁症的发病机制，以及内脏型肥胖、代谢综合征和睡眠障碍等病症。在炎症过程中，应激系统的激活通过诱导Th2偏移，保护机体免受Th1/促炎细胞因子引起的全身性“过度反应”。然而，在某些情况下，应激激素实际上可能通过诱导白细胞介素（IL）-1、IL-6、IL-8、IL-18、肿瘤坏死因子-α和C反应蛋白的产生，以及通过激活促肾上腺皮质激素释放激素/ P物质 - 组胺轴来促进炎症。因此，与“全身抗炎反馈”异常和/或局部促炎因子“过度活跃”相关的功能失调的神经内分泌 - 免疫界面可能在特应性/过敏性和自身免疫性疾病、肥胖、抑郁症和动脉粥样硬化的发病机制中起作用。这些异常以及适应性系统解决炎症的失败会影响个体的幸福感，包括行为参数、生活质量和睡眠，以及代谢和心血管健康指标。这些假设需要进一步研究，但答案应能为各种常见人类免疫相关疾病的潜在机制提供关键见解。
