A menstrual cycle pattern for cytokine levels exists in HIV-positive women: implication for HIV vaginal and plasma shedding

Objectives: To evaluate the effect of the menstrual cycle in HIV-positive w omen on plasma and genital cytokine levels, interrelationships between vagi nal and plasma cytokines, CD4 and CD8 T cell fluctuations, and genital and plasma viral loads. Methods: Plasma and cervicovaginal lavage specimens were collected from 55 HIV-positive women with CD4 cell counts < 350 cells/mul during phases of th e menstrual cycle. Samples were assayed for IL-1 beta, IL-6, IL-4, IL-8, IL -10, TGF beta, TNF alpha, INF gamma, MIP1 alpha, MIP1 beta, RANTES, and TNF R-II using enzyme-linked immunosorbent assays. CD4 and CD8 T cell expressio n was evaluated by flow cytometry. Repeated measures regression models were used to assess the effect of the menstrual cycle on cytokines and viral lo ad. Multivariate repeated regression models were used to assess the correla tion among selected cytokines and between selected cytokines and HIV viral load. Results: Vaginal IL-1 beta, IL-4, IL-6, IL-8, IL-10, MIP1 beta, RANTES, TGF beta, and TNFR-II were significantly elevated during menses but were not a ltered during other phases. Plasma cytokine levels were not altered during the menstrual cycle. A positive Candida culture increased vaginal IL-8 duri ng menses, whereas vaginal discharge was associated with a reduction in vag inal IL-4, IL-10, and RANTES. CD4 and CD8 cell numbers did not vary with th e menstrual cycle. Vaginal cytokine levels correlated only with vaginal vir al load, in a sampling method-dependent manner. Conclusion: We provide evidence of elevated vaginal cytokine levels during menses, which appear to regulate vaginal and not plasma HIV shedding, sugge sting that a menstrual cycle pattern exists for cytokine production in HIV- positive women impacting vaginal shedding of HIV. (C) 2001 Lippincott Willi ams & Wilkins.