P40.11
Background: The female reproductive tract (FRT) secretes immune mediators protective against sexually transmitted infections, including HIV. As multiple immune factors in FRT are hormone-responsive, the loss of sex hormones with aging may undermine these defense mechanisms. Women are disproportionately affected by the HIV/AIDS epidemic with heterosexual contact being the major source of new infections. Reports indicate older women are sexually active and often do not use protection as pregnancy is a non-issue. Therefore, investigating the effects of sex hormone-loss on FRT mucosal immune factors is an important target to curtail HIV acquisition.
Methods: CVL samples were collected from 20 HIV-negative premenopausal and postmenopausal women. Each postmenopausal woman provided one sample; each premenopausal woman provided 3 samples collected during proliferative, ovulatory, and secretory stages of menstrual cycle. Commercially available ELISA kits were used to assess the levels of IL-6, IL-8, TNFa, Elafin, HBD-2, MIP3a/CCL20 and SLPI. Samples were analyzed for their anti-HIV activity against HIV-1 IIIB and BaL strains via the TZM-bl assay.
Results: We observed significantly lower levels of critical immune mediators in CVL from postmenopausal women compared to those from premenopausal women: TNFa (11.6 vs 51.5 pg/mL), MIP3a (1.0 vs 93.8 pg/mL), SLPI (39.6 vs 239.2 pg/mL) and HBD-2 (626 vs 6821 pg/mL). Levels of IL-6 and IL-8 displayed a trend toward lower levels in postmenopausal samples whereas Elafin levels remained unchanged. Inhibition of HIV-1 infection was observed for X4/IIIB and R5/BaL strains in both pre and postmenopausal samples with inhibition of BaL stronger in premenopausal samples (54.2 vs 37.6%).
Conclusions: Our findings indicate that levels of critical mucosal immune factors and anti-HIV-1 activity in CVLs are affected by the hormonal status of healthy HIV-negative women. This indicates the need for specific therapeutic interventions to boost genital tract immunity against HIV in older women.
