title: The contraceptive depot medroxyprogesterone acetate impairs mycobacterial control and inhibits cytokine secretion in mice infected with Mycobacterium tuberculosis.
abstract: The contraceptive depot medroxyprogesterone acetate (DMPA), with progestin as the single active compound, possesses selective glucocorticoid activity and can alter the expression of glucocorticoid receptor-regulated genes. We therefore propose that pharmacological doses of DMPA used for endocrine therapy could have significant immune modulatory effects and impact on susceptibility to, as well as clinical manifestation and outcome of, infectious diseases. We investigated the effect of contraceptive doses of DMPA in two different murine Mycobacterium tuberculosis models. Multiplex bead array analysis revealed that DMPA altered serum cytokine levels of tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), and interleukin 10 (IL-10) in C57BL/6 mice and gamma interferon (IFN-γ) in BALB/c mice. DMPA also suppressed antigen-specific production of TNF-α, G-CSF, IL-10, and IL-6 and induced the production of IP-10 in C57BL/6 mice. In BALB/c mice, DMPA altered the antigen-specific secretion of IFN-γ, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and monocyte chemotactic protein 1 (MCP-1). Furthermore, we show that C57BL/6 mice treated with doses of DMPA, which result in serum concentrations similar to those observed in contraceptive users, have a significantly higher bacterial load in their lungs. Our data show for the first time that DMPA impacts tuberculosis (TB) disease severity in a mouse model and that the effects of this contraceptive are not confined to infections of the genital tract. This could have major implications for the contraceptive policies not only in developing countries like South Africa but also worldwide.
authors: DST/NRF Centre of Excellence for Biomedical TB Research/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors: Léanie
authors: L
authors: Kleynhans
authors: Nelita
authors: N
authors: Du Plessis
authors: Nasiema
authors: N
authors: Allie
authors: Muazzam
authors: M
authors: Jacobs
authors: Martin
authors: M
authors: Kidd
authors: Paul D
authors: PD
authors: van Helden
authors: Gerhard
authors: G
authors: Walzl
authors: Katharina
authors: K
authors: Ronacher
mesh_terms: D000818:Animals; D003270:Contraceptive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D007165:Immunosuppression Therapy; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D003270:Contraceptive Agents; D016207:Cytokines; D007155:Immunologic Factors; D017258:Medroxyprogesterone Acetate
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