The influence of sex steroid hormones in the immunopathology of experimental pulmonary tuberculosis

BINI E; MATA D; MARQUINA B; BARRIOS PAYAN J; COLUCCI DJ; CRUZ F; ZATARAIN ZL; ALFONSECA E; ROMANO M; BOTTASSO O; HERNANDEZ PANDO R

Puebla

Congreso; IV Iberoamerican Congress on Neuroimmunomodulation and I Mexican Congress on Neuroimmunoendocrinology. Puebla-México Oct. 29th-Nov.1st, 2013; Pp 103; 2013

ISNIM

In almost all countries, especially developing ones, the relation between men and women suffering pulmonary tuberculosis (TB) is 7/3 in favor to the male, a difference commonly attributed to biological and epidemiological factors. Since the biological perspective, steroid sex hormones can be a significant factor for this gender difference. Testosterone impairs macrophage activation and proinflammatory cytokines production, while estrogens are considered as proinflammatory mediators inducer. The aim of this work was to compare the evolution of the disease in male and female mice using a model of progressive pulmonary TB. Groups of eight- weeks old BALB/c mice, male and female were randomized into two groups: castrated or sham-operated. Two weeks after surgery, animals were infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and their lungs were used to determine bacilli loads (colony-forming units), inflammation in different lung compartments, granuloma size and pneumonia extension (automated histomorphometry), cytokine expression (real time PCR), survival and testosterone levels in serum. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female animals. Compared to males, females and castrated males mice exhibited significant higher inflammation in most of all lung compartments, earlier formation of granulomas and pneumonia, while between castrated and non-castrated females in none of lung compartments were observed significant differences. Females and castrated males mice expressed significant higher levels of TNF-a, IFN-g, IL12, iNOS and IL17, especially during the first month of infection (early phase). Serum Testosterone levels of male mice showed peaks in coincidence with moments of maximal inflammation at days 1, 14 and 60 postinfection. When male mice were gonadoctomized during late progressive disease at day 60 post-infection, a significant decrease of bacilli burdens in coexistence with lesser tissue damage and higher expression of TNF-a, IL-12 and IFN-g than control sham mice was seen. Thus, male mice are more susceptible to TB than females. This higher susceptibility was prevented by orchidectomy during early or late infection suggesting that testosterone could be a TB susceptibility factor, probably by its anti-inflammatory and cell-mediated immune suppressive effects.