title: Lower concentrations of chemotactic cytokines and soluble innate factors in the lower female genital tract associated with the use of injectable hormonal contraceptive.
abstract: Progesterone-based injectable hormonal contraceptives (HCs) potentially modulate genital barrier integrity and regulate the innate immune environment in the female genital tract, thereby enhancing the risk of STIs or HIV infection. We investigated the effects of injectable HC use on concentrations of inflammatory cytokines and other soluble factors associated with genital epithelial repair and integrity. The concentrations of 42 inflammatory, regulatory, adaptive growth factors and hematopoietic cytokines, five matrix metalloproteinases (MMPs), and four tissue inhibitors of metalloproteinases (TIMPs) were measured in cervicovaginal lavages (CVLs) from 64 HIV-negative women using injectable HCs and 64 control women not using any HCs, in a matched case-control study. There were no differences between groups in the prevalence of bacterial vaginosis (BV; Nugent score ≥7), or common sexually transmitted infections (STIs). In multivariate analyses adjusting for condom use, sex work status, marital status, BV and STIs, median concentrations of chemokines (eotaxin, MCP-1, MDC), adaptive cytokines (IL-15), growth factors (PDGF-AA) and a metalloproteinase (TIMP-2) were significantly lower in CVLs from women using injectable HCs than controls. In addition, the pro-inflammatory cytokine IL-12p40 and the chemokine fractalkine were less likely to have detectable levels in women using injectable HCs compared with those not using HCs. We conclude that injectable HC use was broadly associated with an immunosuppressive female genital tract innate immune profile. While the relationship between injectable HC use and STI or HIV risk is yet to be resolved, our data suggest that the effects of injectable HCs were similar in STI-positive and STI-negative participants.
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Sinaye
authors.initials: S
authors.lastname: Ngcapu
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School Cape Town, South Africa.
authors.forename: Lindi
authors.initials: L
authors.lastname: Masson
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Sengeziwe
authors.initials: S
authors.lastname: Sibeko
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Lise
authors.initials: L
authors.lastname: Werner
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Lyle R
authors.initials: LR
authors.lastname: McKinnon
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Muki
authors.initials: M
authors.lastname: Shey
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Natasha
authors.initials: N
authors.lastname: Samsunder
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa; Department of Epidemiology, Mailman School of Public Health, Columbia University, NY, USA.
authors.forename: Salim Abdool
authors.initials: SA
authors.lastname: Karim
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa; Department of Epidemiology, Mailman School of Public Health, Columbia University, NY, USA.
authors.forename: Quarraisha Abdool
authors.initials: QA
authors.lastname: Karim
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School Cape Town, South Africa; National Health Laboratory Service, South Africa. Electronic address: Jo-ann.Passmore@uct.ac.za.
authors.forename: Jo-Ann S
authors.initials: JA
authors.lastname: Passmore
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002584:Cervix Uteri / Q000276:immunology* / Q000382:microbiology; D018925:Chemokines / Q000276:immunology*; D017364:Collagenases / Q000276:immunology*; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000276:immunology*; D014621:Vagina / Q000276:immunology* / Q000382:microbiology; D016585:Vaginosis, Bacterial / Q000453:epidemiology* / Q000276:immunology
chemical_list: D018925:Chemokines; D003271:Contraceptive Agents, Female; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases
keywords: Cytokines; DMPA; Hormone contraceptives; MMP; Net-EN; TIMP