Tsatsoulis Agathocles
Department of Endocrinology, University of Ioannina, 45110, Ioannina, Greece.
Ann N Y Acad Sci. 2006 Nov;1088:382-95. doi: 10.1196/annals.1366.015.
During stress, activation of the hypothalamic-pituitary-adrenal axis and the sympathoadrenal system leads to increased secretion of glucocorticoids and catecholamines, respectively, in order to maintain homeostasis. Recent evidence suggests that stress hormones, acting on antigen-presenting immune cells, may influence the differentiation of bipotential T helper (Th) cells away from Th1 and toward a Th2 phenotype. This results in suppression of cellular immunity and potentiation of humoral immunity. Thyroid autoimmunity is clinically expressed as Hashimoto's thyroiditis (HT) and its variants (sporadic or postpartum thyroiditis) or as Grave's disease (GD). The different phenotypic expression of thyroid autoimmunity is largely dependent on the balance of Th1 versus Th2 immune response. A predominantly Th1-mediated immune activity may promote apoptotic pathways on thyroid follicular cells leading to thyroid cell destruction and HT. Conversely, predominance of Th2-mediated immune response may induce antigen-specific B lymphocytes to produce anti-TSH receptor (TSHr) antibodies causing GD. The weight of evidence from epidemiological and case-control studies supports an association between stress and GD. On the other hand, there is little information available on the effect of stress on HT, but there is evidence for an increase in postpartum thyroiditis, following the cellular immune suppressive effect of pregnancy. Whether stress has a causative effect on GD remains elusive. Circumstantial evidence supports the hypothesis that stress may influence the clinical expression of thyroid autoimmunity in susceptible individuals favoring the development of GD by shifting the Th1-Th2 balance away for Th1 and toward Th2. Conversely, recovery from stress or the immune suppressive effect of pregnancy may induce a Th2 to Th1 "return shift" leading to autoimmune (sporadic) or postpartum thyroiditis, respectively.
在应激状态下，下丘脑 - 垂体 - 肾上腺轴和交感 - 肾上腺系统的激活分别导致糖皮质激素和儿茶酚胺分泌增加，以维持体内平衡。最近的证据表明，作用于抗原呈递免疫细胞的应激激素可能会影响双潜能T辅助（Th）细胞从Th1表型向Th2表型的分化。这导致细胞免疫受到抑制，体液免疫增强。甲状腺自身免疫在临床上表现为桥本甲状腺炎（HT）及其变体（散发性或产后甲状腺炎）或格雷夫斯病（GD）。甲状腺自身免疫不同的表型表达很大程度上取决于Th1与Th2免疫反应的平衡。主要由Th1介导的免疫活动可能会促进甲状腺滤泡细胞的凋亡途径，导致甲状腺细胞破坏和HT。相反，Th2介导的免疫反应占主导地位可能会诱导抗原特异性B淋巴细胞产生抗促甲状腺激素受体（TSHr）抗体，从而引发GD。流行病学和病例对照研究的大量证据支持应激与GD之间存在关联。另一方面，关于应激对HT影响的信息很少，但有证据表明，由于妊娠的细胞免疫抑制作用，产后甲状腺炎有所增加。应激是否对GD有因果关系仍不清楚。间接证据支持这样的假设，即应激可能会影响易感个体中甲状腺自身免疫的临床表达，通过将Th1-Th2平衡从Th1转向Th2，有利于GD的发展。相反，应激恢复或妊娠的免疫抑制作用可能分别诱导Th2向Th1的“回移”，导致自身免疫性（散发性）或产后甲状腺炎。
