title: Medroxyprogesterone acetate alters Mycobacterium bovis BCG-induced cytokine production in peripheral blood mononuclear cells of contraceptive users.
abstract: Most individuals latently infected with Mycobacterium tuberculosis (M.tb) contain the infection by a balance of effector and regulatory immune responses. This balance can be influenced by steroid hormones such as glucocorticoids. The widely used contraceptive medroxyprogesterone acetate (MPA) possesses glucocorticoid activity. We investigated the effect of this hormone on immune responses to BCG in household contacts of active TB patients. Multiplex bead array analysis revealed that MPA demonstrated both glucocorticoid and progestogenic properties at saturating and pharmacological concentrations in peripheral blood mononuclear cells (PBMCs) and suppressed antigen specific cytokine production. Furthermore we showed that PBMCs from women using MPA produced significantly lower levels of IL-1α, IL-12p40, IL-10, IL-13 and G-CSF in response to BCG which corresponded with lower numbers of circulating monocytes observed in these women. Our research study is the first to show that MPA impacts on infections outside the genital tract due to a systemic effect on immune function. Therefore MPA use could alter susceptibility to TB, TB disease severity as well as change the efficacy of new BCG-based vaccines, especially prime-boost vaccine strategies which may be administered to adult or adolescent women in the future.
authors.affiliation: Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Léanie
authors.initials: L
authors.lastname: Kleynhans
authors.forename: Nelita
authors.initials: N
authors.lastname: Du Plessis
authors.forename: Gillian F
authors.initials: GF
authors.lastname: Black
authors.forename: André G
authors.initials: AG
authors.lastname: Loxton
authors.forename: Martin
authors.initials: M
authors.lastname: Kidd
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.forename: Katharina
authors.initials: K
authors.lastname: Ronacher
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects*; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D018793:Interleukin-13; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D017258:Medroxyprogesterone Acetate