Estela Isabel Bini1, Luciano D'Attilio2, Brenda Marquina-Castillo3, Dulce Mata-Espinosa3, Ariana Díaz2, Ricardo Marquez-Velasco4, Octavio Ramos-Espinosa3, Armando Gamboa-Domínguez3, Maria Luisa Bay2, Rogelio Hernández-Pando3, Oscar Bottasso2. 1. Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán" (INCMNSZ), Vasco de Quiroga 15, Tlapan, México City, Mexico; Institute of Clinical and Experimental Immunology of Rosario, IdICER (CONICET-UNR), Suipacha 590, Rosario, Argentina. Electronic address: estelabini@yahoo.com.ar. 2. Institute of Clinical and Experimental Immunology of Rosario, IdICER (CONICET-UNR), Suipacha 590, Rosario, Argentina. 3. Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán" (INCMNSZ), Vasco de Quiroga 15, Tlapan, México City, Mexico. 4. Department of Immunology, National Institute of Cardiology "Dr Ignacio Chavez", Juan Badiano 1, Tlapan, México City, Mexico.
Abstract
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-α, IFN-γ, TGF-β, 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-1β, TNF-α, IL-6 and IFN-γ. The TM3 mouse Leydig cell line was incubated with recombinants TNF-α, IFN-γ and TGF-β, 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-γ, IL-6 and TGF-β levels. Testicular histological sections showed abundant presence of IL-1β, TNF-α, IL-6 and IFN-γ 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.
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 TBpatients. METHODS: Plasma samples from 36 active untreated pulmonary TB male patients were used to determine TNF-α, IFN-γ, TGF-β, 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 TBpatients and similar age (40 ± 16,8 years). Testicular histological samples from necropsies of patients dying from TB were immune-stained for IL-1β, TNF-α, IL-6 and IFN-γ. The TM3 mouse Leydig cell line was incubated with recombinants TNF-α, IFN-γ and TGF-β, 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-γ, IL-6 and TGF-β levels. Testicular histological sections showed abundant presence of IL-1β, TNF-α, IL-6 and IFN-γ 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.
Authors: Sara Duarte Gutierrez; Samuel da Silva Aguiar; Lucas Pinheiro Barbosa; Patrick Anderson Santos; Larissa Alves Maciel; Patrício Lopes de Araújo Leite; Thiago Dos Santos Rosa; Lysleine Alves de Deus; John Eugene Lewis; Herbert Gustavo Simões Journal: J Clin Transl Res Date: 2021-07-16