title: The implication of pro-inflammatory cytokines in the impaired production of gonadal androgens by patients with pulmonary tuberculosis.
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.
authors.affiliation: 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.
authors.forename: Estela Isabel
authors.initials: EI
authors.lastname: Bini
authors.affiliation: Institute of Clinical and Experimental Immunology of Rosario, IdICER (CONICET-UNR), Suipacha 590, Rosario, Argentina.
authors.forename: Luciano
authors.initials: L
authors.lastname: D'Attilio
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán" (INCMNSZ), Vasco de Quiroga 15, Tlapan, México City, Mexico.
authors.forename: Brenda
authors.initials: B
authors.lastname: Marquina-Castillo
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán" (INCMNSZ), Vasco de Quiroga 15, Tlapan, México City, Mexico.
authors.forename: Dulce
authors.initials: D
authors.lastname: Mata-Espinosa
authors.affiliation: Institute of Clinical and Experimental Immunology of Rosario, IdICER (CONICET-UNR), Suipacha 590, Rosario, Argentina.
authors.forename: Ariana
authors.initials: A
authors.lastname: Díaz
authors.affiliation: Department of Immunology, National Institute of Cardiology "Dr Ignacio Chavez", Juan Badiano 1, Tlapan, México City, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Marquez-Velasco
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán" (INCMNSZ), Vasco de Quiroga 15, Tlapan, México City, Mexico.
authors.forename: Octavio
authors.initials: O
authors.lastname: Ramos-Espinosa
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán" (INCMNSZ), Vasco de Quiroga 15, Tlapan, México City, Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Gamboa-Domínguez
authors.affiliation: Institute of Clinical and Experimental Immunology of Rosario, IdICER (CONICET-UNR), Suipacha 590, Rosario, Argentina.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Bay
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán" (INCMNSZ), Vasco de Quiroga 15, Tlapan, México City, Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.affiliation: Institute of Clinical and Experimental Immunology of Rosario, IdICER (CONICET-UNR), Suipacha 590, Rosario, Argentina.
authors.forename: Oscar
authors.initials: O
authors.lastname: Bottasso
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood*; D000818:Animals; D016022:Case-Control Studies; D002460:Cell Line; D016207:Cytokines / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood* / Q000494:pharmacology; D007985:Leydig Cells / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D012720:Severity of Illness Index; D013737:Testis / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000097:blood*; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000473:pathology
chemical_list: D000728:Androgens; D016207:Cytokines; D018836:Inflammation Mediators; D013739:Testosterone
keywords: Cytokines; Gonadal steroids; Testosterone; Tuberculosis