Sex differences in glucocorticoid sensitivity of proinflammatory cytokine production after psychosocial stress
Sex differences in glucocorticoid sensitivity of proinflammatory cytokine production after psychosocial stress
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DOI：
10.1097/00006842-200111000-00016
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发表时间：
2001-11-01
影响因子：
3.3
通讯作者：
Kirschbaum, C
中科院分区：
文献类型：
--
作者：
Rohleder, N;Schommer, NC;Kirschbaum, C
目的：男性和女性在与免疫系统相关的疾病的易感性方面存在显著差异。这些性别差异被认为是由下丘脑-垂体-肾上腺（HPA）和下丘脑-垂体-性腺（HPG）轴的功能相互作用介导的。这种相互作用的潜在机制是相关靶组织对糖皮质激素（GC）的敏感性。因此，本研究的目的是研究心理社会应激和HPA轴激活对男性和女性促炎细胞因子产生的GC敏感性的影响。方法：对45名健康受试者进行调查。18名处于月经周期黄体期的女性和27名男性接受了心理社会压力测试（特里尔社会压力测试）。暴露于压力源后，反复测量唾液游离皮质醇水平。通过地塞米松抑制脂多糖刺激的白细胞介素-6和肿瘤坏死因子- α的产生，体外评估GC敏感性。结果：压力测试诱导唾液游离皮质醇显著增加，男女无显著差异。相比之下，GC敏感性和脂多糖刺激的细胞因子产生显示出较大的性别差异。应激后1小时，男性GC敏感性明显增高。而女性的GC敏感性明显下降。同样，脂多糖诱导的细胞因子的产生在男性应激反应中减少，而在女性应激反应中增加。结论：这些结果表明，尽管男性和女性（在黄体期研究）对社会心理压力的游离皮质醇反应相似，但性别可能通过调节促炎细胞因子产生的GC敏感性对免疫系统产生不同的影响。
Objective: Men and women show marked differences in susceptibility to disorders related to the immune system. These gender differences have been proposed to be mediated by functional interactions of the hypothalamuspituitary-adrenal (HPA) and hypothalamus-pituitary-gonadal (HPG) axes. A potential mechanism involved in this interaction is the glucocorticoid (GC) sensitivity of relevant target tissues for GC. Therefore, the aim of the study reported here was to investigate the impact of psychosocial stress and HPA axis activation on the GC sensitivity of proinflammatory cytokine production in men and women. Methods: A total of 45 healthy subjects were investigated. Eighteen women in the luteal phase of their menstrual cycle and 27 men were exposed to a psychosocial stress test (Trier Social Stress Test). Salivary free cortisol levels were measured repeatedly after exposure to the stressor. GC sensitivity was assessed in vitro by dexamethasone inhibition of lipopolysaccharide-stimulated production of interleukin-6 and tumor necrosis factor-alpha. Results: The stress test induced significant increases in salivary free cortisol with no significant differences between men and women. In contrast, GC sensitivity and lipopolysaccharide-stimulated cytokine production showed large gender differences. In men GC sensitivity was markedly increased 1 hour after stress. whereas GC sensitivity decreased significantly in women. Similarly, lipopolysaccharide-induced cytokine production decreased in response to stress in men but increased in women. Conclusions: These results demonstrate that despite similar free cortisol responses of men and women (studied in the luteal phase) to psychosocial stress, gender may exert differential effects on the immune system by modulating GC sensitivity of proinflammatory cytokine production.