EFFECTS OF HORMONES ON MUCOSAL IMMUNE MEDIATORS ACROSS THE MENSTRUAL CYCLE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The female genital tract is immunologically unique because it must be tolerant to spermatozoa, pregnancy and vaginal flora, but also protect the host from pathogen challenge. Moreover, hormonal fluctuations may modify the mucosal environment. Cytokines, chemokines, immunoglobulins, defensins and other proteins provide a defense against sexually transmitted infections (STI), but also may be modified in the setting of infection or in response to vaginal application of microbicides, drugs in development to prevent HIV and other STI. Little is known about the impact of endogenous and exogenous hormones on the relative concentration of individual factors in cervicovaginal secretions and the cumulative effects of any observed changes on mucosal immunity. The proposed study will address this gap and provide critical data for ongoing and future studies that address the impact of microbicides on levels of cytokines, chemokines or other proteins and cell populations in cervicovaginal secretions. We propose to measure the changes in immune mediators in two groups of women, 18-35 years of age. One group will be using hormonal contraception and the other group will have regular menstrual periods. The biological significance of any observed changes will be assessed by examining the innate antimicrobial activity of the fluid using well-established assays. Hypothesis: To establish the variability in cytokines, chemokines, defensins, secretory leukocyte protease inhibitor (SLPI), immunoglobulins and lactoferrin in cervicovaginal fluids in a cohort of women 18-35 years of age at each phase of the menstrual cycle compared with women on oral contraceptives. To establish variability in immune cell population in cytobrush samples obtained from a cohort of women 18-35 years of age at each phase of the menstrual cycle compared with women on oral contraceptives . To determine if changes in mucosal immune mediators across the menstrual cycle or in women using oral contraceptives are associated with alterations in intrinsic antimicrobial activity