The implication of pro-inflammatory cytokines in the impaired production of gonadal androgens by patients with pulmonary tuberculosis

BINI E; D´ATTILIO L; MARQUINA CASTILLO B; MATA ESPINOSA D; DIAZ A; MARQUEZ VELASCO R; GAMBOA DOMINGUEZ A; BAY ML; HERNANDEZ PANDO R; BOTTASSO O

Riviera Nayarit

Congreso; II Congreso de la Sociedad Mexicana de Neuroinmunoendocrinología; 2015

Sociedad Mexicana de Neuroinmunoendocrinología

Background: The chronic nature of tuberculosis and the protracted immuno-inflammatory reactions are implied in a series of metabolic and immune-endocrine changes accompanying the disease. We explored components from the hypothalamous-pituitary-gonadal axis and their relationship with cytokines involved in disease immunopathology, in male TB patients. Methods: Plasma samples from 36 active untreated pulmonary TB male patients were used to determine TNF-a, IFN-g, TGF-beta, IL-6, cortisol, dehydroepiandrosterone, testosterone, progesterone, estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by ELISA. Healthy controls corresponded to 21 volunteers without contact with TB patients and similar age (40+/- 16,8 years). Testicular histological samples from necropsies of patients dying from TB were immune-stained for IL-1beta, TNF-a, IL-6 and IFN-g. The TM3 mouse Leydig cell line was incubated with recombinants TNF-a, IFN-g and TGF-B, supernatants were collected and used to measure testosterone by ELISA.Results: Patients showed decreased levels of testosterone in presence of high amounts of LH, together with augmented IFN-g, IL-6 and TGF-beta levels. Testicular histological sections showed abundant presence of IL-1beta, TNF-alpha, IL-6 and IFN-g in interstitial macrophages, Sertoli cells and some spermatogonia. In vitro treatment of Leydig cells with these cytokines led to a remarkable reduction of testosterone production.