Rey Adriana Del, Mahuad Carolina V, Bozza Verónica V, Bogue Cristina, Farroni Miguel A, Bay María Luisa, Bottasso Oscar A, Besedovsky Hugo O
Institut für Physiologie und Pathophysiologie, 35037 Marburg, Germany.
Brain Behav Immun. 2007 Feb;21(2):171-9. doi: 10.1016/j.bbi.2006.06.005. Epub 2006 Aug 4.
Endocrine responses during chronic infections such as lung tuberculosis are poorly characterized. Hormonal changes are likely to occur since some of the cytokines produced during this disease could affect endocrine mechanisms that, in turn, influence the course of infectious/inflammatory processes. A main purpose of this work was to study endocrine responses involving pituitary, adrenal, gonadal, and thyroid hormones in parallel to IFN-gamma, IL-10, and IL-6 levels in tuberculosis patients with different degree of pulmonary involvement. We have also studied whether products derived from peripheral immune cells obtained from the patients can affect the in vitro production of adrenal steroids. The population studied comprised HIV-negative newly diagnosed, untreated male patients with mild, moderate, and advanced lung tuberculosis, and matched, healthy controls. IFN-gamma, IL-10, and IL-6 levels were elevated in patients with tuberculosis. Dehydroepiandrosterone and testosterone levels were profoundly decreased and growth hormone levels were markedly elevated in patients, in parallel to modest increases in cortisol, estradiol, prolactin, and thyroid hormone concentrations. Supernatants of peripheral blood mononuclear cells obtained from the patients and stimulated in vitro with Mycobacterium tuberculosis antigens significantly inhibited dehydroepiandrosterone secretion by the human adrenal cell line NCI-H295-R. These results support the hypothesis that at least some of the endocrine changes observed in the patients may be mediated by endogenous cytokines. The endocrine profile of tuberculosis patients would favor a reduction of protective cell-mediated immunity and an exacerbation of inflammation leading to perpetuation of the lung injury and to the hypercatabolic condition that characterizes this disease.
诸如肺结核之类的慢性感染期间的内分泌反应目前尚无充分的特征描述。由于该疾病期间产生的一些细胞因子可能会影响内分泌机制,而内分泌机制反过来又会影响感染/炎症过程的进程,因此很可能会发生激素变化。这项工作的主要目的是研究垂体、肾上腺、性腺和甲状腺激素相关的内分泌反应,同时研究不同程度肺部受累的肺结核患者体内的干扰素-γ、白细胞介素-10和白细胞介素-6水平。我们还研究了从患者获取的外周免疫细胞衍生的产物是否会影响体外肾上腺类固醇的产生。所研究的人群包括新诊断的、未经治疗的HIV阴性男性患者,他们患有轻度、中度和重度肺结核,以及相匹配的健康对照者。肺结核患者体内的干扰素-γ、白细胞介素-10和白细胞介素-6水平升高。患者体内的脱氢表雄酮和睾酮水平大幅下降,生长激素水平显著升高,同时皮质醇、雌二醇、催乳素和甲状腺激素浓度略有升高。从患者获取的外周血单个核细胞的上清液,在体外用结核分枝杆菌抗原刺激后,显著抑制了人肾上腺细胞系NCI-H295-R分泌脱氢表雄酮。这些结果支持这样一种假说,即患者体内观察到的至少部分内分泌变化可能是由内源性细胞因子介导的。肺结核患者的内分泌特征可能会导致保护性细胞介导免疫的降低以及炎症的加剧,从而导致肺损伤持续存在,并导致该疾病所特有的分解代谢亢进状态。