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

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-alpha, IFN-gamma, 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-1 beta, TNF-alpha, IL-6 and IFN-gamma. The TM3 mouse Leydig cell line was incubated with recombinants TNF-alpha, IFN-gamma and TGF-beta, 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-gamma, IL-6 and TGF-beta levels. Testicular histological sections showed abundant presence of IL-1 beta, TNF-alpha, IL-6 and IFN-gamma 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. (C) 2015 Elsevier Ltd. All rights reserved.