Bini Estela Isabel, Mata Espinosa Dulce, Marquina Castillo Brenda, Barrios Payán Jorge, Colucci Darío, Cruz Alejandro Francisco, Zatarain Zyanya Lucía, Alfonseca Edgar, Pardo Marta Romano, Bottasso Oscar, Hernández Pando Rogelio
Experimental Pathology Section. Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", México City, México; Immunology Institute, Medical Sciences Faculty, Santa Fe, Rosario, Argentina.
Experimental Pathology Section. Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", México City, México.
PLoS One. 2014 Apr 10;9(4):e93831. doi: 10.1371/journal.pone.0093831. eCollection 2014.
The relation between men and women suffering pulmonary tuberculosis is 7/3 in favor to males. Sex hormones could be a significant factor for this difference, considering that testosterone impairs macrophage activation and pro-inflammatory cytokines production, while estrogens are proinflammatory mediator's inducer. The aim of this work was to compare the evolution of tuberculosis in male and female mice using a model of progressive disease. BALB/c mice, male and female were randomized into two groups: castrated or sham-operated, and infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and in their lungs were determined bacilli loads, inflammation, cytokines expression, survival and testosterone levels in serum. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female and castrated male animals. Compared to males, females and castrated males exhibited significant higher inflammation in all lung compartments, earlier formation of granulomas and pneumonia, while between castrated and non-castrated females there were not significant differences. Females and castrated males expressed significant higher TNF-α, IFN γ, IL12, iNOS and IL17 than non-castrated males during the first month of infection. Serum Testosterone of males showed higher concentration during late infection. Orchidectomy at day 60 post-infection produced a significant decrease of bacilli burdens in coexistence with higher expression of TNFα, IL-12 and IFNγ. Thus, male mice are more susceptible to tuberculosis than females and this was prevented by castration suggesting that testosterone could be a tuberculosis susceptibility factor.
患肺结核的男性与女性的比例为7比3，男性更易患病。考虑到睾酮会损害巨噬细胞的激活和促炎细胞因子的产生，而雌激素是促炎介质的诱导剂，性激素可能是造成这种差异的一个重要因素。这项研究的目的是使用一种进行性疾病模型来比较雄性和雌性小鼠肺结核的病情发展。将雄性和雌性BALB/c小鼠随机分为两组：去势组或假手术组，并通过气管内途径用高剂量的结核分枝杆菌H37Rv菌株进行感染。在不同时间点对小鼠实施安乐死，并测定其肺部的杆菌载量、炎症、细胞因子表达、存活率以及血清中的睾酮水平。未去势的雄性小鼠在疾病后期的死亡率和杆菌负荷显著高于雌性和去势雄性动物。与雄性相比，雌性和去势雄性在所有肺叶中的炎症反应显著更高，肉芽肿和肺炎形成更早，而去势雌性和未去势雌性之间没有显著差异。在感染的第一个月，雌性和去势雄性表达的肿瘤坏死因子-α、干扰素γ、白细胞介素12、诱导型一氧化氮合酶和白细胞介素17显著高于未去势雄性。雄性小鼠血清睾酮在感染后期浓度更高。感染后60天进行睾丸切除可使杆菌负荷显著降低，同时肿瘤坏死因子α、白细胞介素-12和干扰素γ的表达更高。因此，雄性小鼠比雌性小鼠更容易感染肺结核，而去势可预防这种情况，这表明睾酮可能是一个肺结核易感性因素。
