Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases
Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases
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DOI：
10.1196/annals.1351.006
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发表时间：
2006-01-01
期刊：
影响因子：
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通讯作者：
Elenkov, Ilia
中科院分区：
文献类型：
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作者：
Calcagni, Emanuele;Elenkov, Ilia
压力和健康结果之间的关联现在已经被仔细记录，但压力具体影响疾病易感性和结果的机制仍然知之甚少。最近的证据表明，糖皮质激素（GC）和儿茶酚胺（CA），主要的应激激素，抑制全身IL-12，TNF-α，和INF-γ，但上调IL-10，IL-4，和TGF-β的生产。因此，在免疫和炎症反应期间，通过诱导Th 2转变激活应激系统可以保护生物体免受T辅助淋巴细胞1（Th 1）/促炎细胞因子的系统性“过冲”。然而，在某些局部反应和某些条件下，应激激素实际上可能通过诱导IL-1、IL-6、IL-8、IL-18、TNF-α和CRP产生，以及通过激活促肾上腺皮质激素释放激素（CRH）/P物质（SP）-组胺轴，促进炎症。自身免疫、慢性感染、重度抑郁症和动脉粥样硬化的特征在于促/抗炎和Th 1/Th 2细胞因子平衡失调。因此，过度活跃或活动不足的应激系统，以及与“全身抗炎反馈”和/或局部促炎因子的“过度活跃”异常相关的功能失调的神经内分泌-免疫界面可能有助于这些疾病的发病机制。与应激系统活性的显著变化相关的病症，例如急性或慢性应激、慢性应激的停止、妊娠和产后期、或类风湿性关节炎（RA），通过调节全身或局部促炎/抗炎和Th 1/Th 2细胞因子平衡，可抑制或增强疾病活性和/或进展。因此，应激诱导的先天性和Th细胞因子产生的抑制或上调可能代表应激影响疾病易感性、活性和各种免疫相关疾病的结果的重要机制。
Associations between stress and health outcomes have now been carefully documented, but the mechanisms by which stress specifically influences disease susceptibility and outcome remain poorly understood. Recent evidence indicates that glucocorticoids (GCs) and catecholamines (CAs), the major stress hormones, inhibit systemically IL-12, TNF-alpha, and INF-gamma, but upregulate IL-10, IL-4, and TGF-beta production. Thus, during an immune and inflammatory response, the activation of the stress system, through induction of a Th2 shift may protect the organism from systemic "overshooting" with T helper lymphocyte 1 (Th1)/proinflammatory cytokines. In certain local responses and under certain conditions, however, stress hormones may actually facilitate inflammation, through induction of IL-1, IL-6, IL-8, IL-18, TNF-alpha, and CRP production, and through activation of the corticotropin-releasing hormone (CRH)/substance P(SP)-histamine axis. Autoimmunity, chronic infections, major depression, and atherosclerosis are characterized by a dysregulation of the pro/anti-inflammatory and Th1/Th2 cytokine balance. Thus, hyperactive or hypoactive stress system, and a dysfunctional neuroendocrine-immune interface associated with abnormalities of the "systemic anti-inflammatory feedback" and/or "hyperactivity" of the local proinflarnmatory factors may contribute to the pathogenesis of these diseases. Conditions that are associated with significant changes in stress system activity, such as acute or chronic stress, cessation of chronic stress, pregnancy and the postpartum period, or rheumatoid arthritis (RA) through modulation of the systemic or local pro/anti-inflammatory and Th1/Th2 cytokine balance, may suppress or potentiate disease activity and/or progression. Thus, stress hormones-induced inhibition or upregulation of innate and Th cytokine production may represent an important mechanism by which stress affects disease susceptibility, activity, and outcome of various immune-related diseases.