title: 16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates chemotherapy-induced bacterial clearance in a model of progressive pulmonary tuberculosis.
abstract: BALB/c mice with pulmonary tuberculosis develop a T helper cell type 1 response that peaks at 3 weeks, temporarily controlling bacterial growth. Then bacterial proliferation recommences, accompanied by increasing interleukin (IL)-4 levels and decreasing interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and inducible nitric oxide synthase (iNOS) levels. These changes mimic those in the human disease. In a previous study, administration of dehydroepiandrosterone (DHEA) beginning on day 60 after infection reversed these changes and protected the mice. However, DHEA is suboptimal for human use, partly because it is readily metabolized into sex steroids. 16alpha-Bromoepiandrosterone (EpiBr; 16alpha -bromo-5alpha -androstan-3beta-ol-17-one) is a synthetic adrenal steroid derivative that does not enter sex steroid pathways. In the present study, when tuberculous BALB/c mice were treated with EpiBr 3 times/week beginning on day 60, inhibition of bacterial proliferation and increased expression of TNF-alpha, IFN-gamma, and iNOS were observed, although decreased expression of IL-4 was also observed. Moreover, when given as an adjunct to conventional chemotherapy, EpiBr enhanced bacterial clearance. Trials for the use of EpiBr in the treatment of human tuberculosis are now justified.
authors.affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.forename: Diana
authors.initials: D
authors.lastname: Aguilar-Leon
authors.forename: Hector
authors.initials: H
authors.lastname: Orozco
authors.forename: Alberto
authors.initials: A
authors.lastname: Serrano
authors.forename: Clarence
authors.initials: C
authors.lastname: Ahlem
authors.forename: Richard
authors.initials: R
authors.lastname: Trauger
authors.forename: Beatrix
authors.initials: B
authors.lastname: Schramm
authors.forename: Chris
authors.initials: C
authors.lastname: Reading
authors.forename: James
authors.initials: J
authors.lastname: Frincke
authors.forename: Graham A W
authors.initials: GA
authors.lastname: Rook
mesh_terms: D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D000738:Androsterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D017024:Chemotherapy, Adjuvant; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D014409:Tumor Necrosis Factor-alpha; C032020:16-bromoepiandrosterone; D000738:Androsterone