Elenkov I J, Chrousos G P, Wilder R L
Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ann N Y Acad Sci. 2000;917:94-105. doi: 10.1111/j.1749-6632.2000.tb05374.x.
Interleukin-12 and tumor necrosis factor (TNF)-alpha promote T-helper (Th) 1 responses and cellular immunity, whereas IL-10 suppresses Th1 activities and stimulates Th2 and humoral immune responses. Recent evidence indicates that glucocorticoids, norepinephrine, epinephrine, histamine, and adenosine inhibit the production of human IL-12 and TNF-alpha, whereas they do not affect or even stimulate the production of IL-10. Through this mechanism these neuroendocrine mediators may cause a selective suppression of Th1 responses and a Th2 shift rather than generalized Th suppression. The substantial Th2-driving force of endogenous stress mediators, as well as histamine and adenosine, can be amplified to a great extent during certain conditions and may play a role in increased susceptibility of the organism to various infections that are normally cleared by Th1 responses. In addition, conditions that contribute to a substantial increase or decrease of local or systemic concentrations of these mediators via modulation of IL-12, TNF alpha/IL-10 balance may also play a role in induction, expression, and progression of certain autoimmune diseases, allergic/atopic reactions, and tumor growth. These conditions include: acute or chronic stress; cessation of chronic stress or chronic hypoactivity of the stress system; severe exercise; serious surgical procedures or traumatic injuries; major burns; severe ischemia or hypoxia; pregnancy and the postpartum period. Thus, better understanding of the neuroendocrine regulation of IL-12, TNF-alpha/IL-10 balance might help the development of new therapeutic strategies for the treatment of Th1- and Th2-mediated human diseases.
白细胞介素-12和肿瘤坏死因子（TNF）-α促进辅助性T（Th）1反应和细胞免疫，而白细胞介素-10抑制Th1活性并刺激Th2和体液免疫反应。最近的证据表明，糖皮质激素、去甲肾上腺素、肾上腺素、组胺和腺苷抑制人白细胞介素-12和TNF-α的产生，而它们不影响甚至刺激白细胞介素-10的产生。通过这种机制，这些神经内分泌介质可能导致Th1反应的选择性抑制和Th2偏移，而不是普遍的Th抑制。内源性应激介质以及组胺和腺苷的强大Th2驱动力在某些情况下可被极大地放大，并可能在机体对通常由Th1反应清除的各种感染的易感性增加中起作用。此外，通过调节白细胞介素-12、TNF-α/白细胞介素-10平衡导致这些介质的局部或全身浓度大幅增加或降低的情况，也可能在某些自身免疫性疾病、过敏/特应性反应和肿瘤生长的诱导、表达和进展中起作用。这些情况包括：急性或慢性应激；慢性应激的停止或应激系统的慢性功能减退；剧烈运动；严重的外科手术或创伤；大面积烧伤；严重缺血或缺氧；妊娠和产后时期。因此，更好地了解白细胞介素-12、TNF-α/白细胞介素-10平衡的神经内分泌调节可能有助于开发治疗Th1和Th2介导的人类疾病的新治疗策略。
