High Levels of Inflammatory Cytokines in the Reproductive Tract of Women with BV and Engaging in Intravaginal Douching: A Cross-Sectional Study of Participants in the Women Interagency HIV Study

Abstract

High levels of inflammatory cytokines in the genital tract suggest mucosal vulnerability and increased risk of HIV and sexually transmitted infection (STI) acquisition. Intravaginal douching is associated with bacterial vaginosis (BV) in women in the United States, and both douching and BV are linked to HIV and STI acquisition. This study evaluates inflammatory cytokines in the genital tract to increase understanding of the effects of both BV and intravaginal douching to the vaginal mucosa. A cross-sectional study of participants in the Miami WIHS investigated 72 reproductive age women (45 HIV⁺ and 27 high-risk HIV^-) who completed intravaginal douching questionnaires and underwent collection of vaginal swabs and cervicovaginal lavages (CVLs). BV was assessed using the Nugent score. Inflammatory cytokines in the CVLs (interleukin [IL]-6, IL-8, IL-1α, IL-1β, soluble intracellular adhesion molecule-1 [sICAM-1], interferon [IFN]α2, chemokine C ligand 5 (CCL5), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP1), tumor necrosis factor alpha (TNFα), and secretory leukocyte protease inhibitor [SLPI]) were measured. Fourteen (19%) women reported intravaginal douching; 24 (33%) had BV. BV, intravaginal douching, and HIV were associated with higher levels of inflammatory cytokines. After controlling for demographic and risk factors and HIV status, women who had BV and douched had higher levels of inflammatory cytokines than those without BV and who did not douche, or who only had BV or only douched. These findings suggest that BV and douching are associated with greater mucosal inflammation and may facilitate HIV acquisition and transmission. Although longitudinal studies are needed to determine temporal associations and causality, interventions to decrease rates of intravaginal douching and BV could significantly decrease women's risks of acquiring STIs and HIV and limit the spread of HIV.

Keywords: bacterial vaginosis; genital cytokines; vaginal douches; women and HIV.

FIG. 1.

Inflammatory cytokines (pg/ml) in women engaging in vaginal douching with and without BV. Box plots report minimum, first interquartile range, median, third interquartile range, and maximum values; the mean is identified by open squares. IL-6: Levels of IL-6 were not significantly different between groups. IL-8: No BV and no douching was significantly different from no BV and douching and BV and douching; no BV and douching was significantly different from BV and no douching and BV and douching; BV and no douching was significantly different than BV and douching (all p < .01). IL-1α, IL-1β, SLPI, MCP1: All groups were significantly different from each other (all p < .05). sICAM-1: No BV and no douching was significantly different from no BV and douching, BV and no douching, and BV and douching; no BV and douching was significantly different from BV and no douching, and BV and douching; BV and no douching was significantly different than BV and douching (all p < .01). IFNα2: No BV and no douching was significantly different from no BV and douching, and BV and no douching (p < .05); no BV and douching was significantly different than BV and no douching. CCL5: No BV and douching was significantly different than BV and no douching and BV and douching (p < .05). VEGF: No BV and no douching was significantly different from no BV and douching, BV and no douching, and BV and douching; no BV and douching was significantly different from BV and douching; BV and no douching was significantly different than BV and douching, and BV and douching (all p < .01). TNFα: No BV and no douching was significantly different than BV and no douching, and BV and douching (p < .01); no BV and douching was significantly different than BV and douching (p < .05). All models controlled for age (continuous), race, condom use, frequency of sexual encounters (continuous), days since last menstruation (continuous), vaginal douching, HIV status, and BV. BV, bacterial vaginosis; CCL5, chemokine C ligand 5; IFN, interferon; MCP1, monocyte chemotactic protein-1; sICAM-1, soluble intracellular adhesion molecule-1; SLPI, secretory leukocyte protease inhibitor; TNFα, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor.