L. Al-harthi et al., A menstrual cycle pattern for cytokine levels exists in HIV-positive women: implication for HIV vaginal and plasma shedding, AIDS, 15(12), 2001, pp. 1535-1543
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.