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

Al‐Harthi, Lena; Kovács, Andrea; Coombs, Robert W.; Reichelderfer, Patricia; Wright, David J.; Cohen, Mardge H.; Cohn, Jonathan; Cu‐Uvin, Susan; Watts, Heather; Lewis, Shirley; Beckner, Suzanne K.; Landay, Alan

doi:10.1097/00002030-200108170-00011

Cited by 65 publications

(58 citation statements)

References 24 publications

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“…This association has not been previously reported, although one study reported that a positive Candida culture was associated with vaginal IL-8 during menses (Al-Harthi et al, 2001). The current study also found a negative relationship between lactobacilli and IL-8.…”

Section: Introductionsupporting

confidence: 56%

“…For example, high vaginal IL-8 concentrations were associated also with amniotic fluid infections in women with preterm labor (Hitti et al, 2001) and in women with bacterial vaginosis (Spandorfer et al, 2001;Wennerholm et al, 1998). Vaginal IL-8 increases were noted also after sexual activity, after exposure to some microbicides and during menses (Al-Harthi et al, 2001;Fichorova, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Vaginal IL-8 levels are positively associated with Candida albicans and inversely with lactobacilli in HIV-infected women

Spear

Zariffard

Cohen

et al. 2008

Journal of Reproductive Immunology

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IL-8/ CXCL8 is induced during infections, but has not been reported for Candida albicans colonization of the female genital tract. Cervicovaginal lavage (CVL) samples were collected from 406 HIV-infected women. IL-8 levels were evaluated by ELISA and compared with levels of C. albicans detected by potassium hydroxide (KOH) and PCR. Levels of lactobacilli, Gardnerella vaginalis and Mycoplasma hominis were also determined by PCR. IL-8 was significantly higher in samples from women with Candida, and regression analysis showed a positive association between IL-8 and Candida. In contrast, there was an inverse relationship between lactobacilli and IL-8. G. vaginalis and M. hominis were not significantly associated with IL-8. This study has shown an association between C. albicans and levels of IL-8 in mucosal genital fluid.

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Section: Introductionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Vaginal IL-8 levels are positively associated with Candida albicans and inversely with lactobacilli in HIV-infected women

Spear

Zariffard

Cohen

et al. 2008

Journal of Reproductive Immunology

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“…Our study is the first to report on the measurement of cervicovaginal cytokine levels to assess urogenital irritation in response to vaginal products in a clinical safety study. Cytokines regulate mucosal immune responses and, in the vaginal environment, may play a critical role in the pathogenesis of HIV-1 and other STIs [17]. N-9-induced vaginal inflammation has been linked to increased HIV activity via IL-1-mediated mechanisms [18].…”

Section: Discussionmentioning

confidence: 99%

Fourteen-day safety and acceptability study of 6% cellulose sulfate gel: a randomized double-blind Phase I safety study

et al. 2006

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TitleFourteen-day safety and acceptability study of 6% cellulose sulfate gel: a randomized double-blind Phase I safety study Abstract Background: Topical microbicides against the human immunodeficiency virus (HIV) 1 that are nonirritating to the female genital epithelium are urgently needed to slow the heterosexual spread of HIV infection. Products that are also effective contraceptives provide additional benefits. Cellulose sulfate (CS) is a noncytotoxic antifertility agent that exhibits in vitro antimicrobial activity against sexually transmitted pathogens, including HIV. Methods: We performed a multicenter, Phase I, placebo-controlled, randomized study to evaluate the genital toxicity of CS. Two cohorts of healthy women used 3.5 ml of 6% CS gel or 3.5 ml of K-Y Jelly, vaginally, bid, for 14 days. The first cohort was sexually abstinent, and the second cohort was sexually active. Results: CS was associated with only a slightly higher odds ratio (OR) of symptoms of minor urogenital irritation compared to the inactive lubricant K-Y Jelly (OR = 2.02, 95% confidence interval = 0.90-4.53). In addition, there were minor shifts in some genital flora, but there was no evidence of greater inflammation as evidenced by few colposcopic findings, decreased influx of polymorphonuclear cells and minimal changes in proinflammatory cytokines. Moreover, both products appeared acceptable to most women. Product leakage was identified as more of a problem in sexually abstinent women, but less so in women using the product for sexual intercourse, as would be the case in actual practice. Conclusion: CS was safe for twice-daily use for 14 days. CS is appropriate for future studies in effectiveness trials. D

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“…20 Secretion of mannosebinding lectin, a molecule in the complement system that plays a critical role in host protection, from vaginal epithelial cells is increased in the LUT phase of the menstrual cycle. 49 Other investigations found that CV immune mediators did not change based on the menstrual cycle (e.g., IL-10, TNF-a, IL-8, RANTES, and TNFR II), 19,26,50 but were higher during menstruation. 26,50 Genital tract cytokines have also been shown to vary based on clinical factors, such as cervical ectopy, inflammation, and sexual activity.…”

Section: No Significant Differences In Vaginal Immune Cells Between Fmentioning

confidence: 98%

“…18 However, there is a paucity of data regarding the effect of the menstrual cycle on immune cell recruitment and activation in the lower reproductive tract, including the ectocervix and vagina, 19,20 with some studies showing no changes in CD4 and CCR5-positive cells, based on the menstrual cycle, in ectocervical explants. 21 Previous studies regarding the effect of endogenous hormones on mucosal HIV targets in the lower genital tract have been done primarily with explants obtained from women undergoing elective surgeries such as hysterectomies [21][22][23][24][25] or among small cohorts of women in a longitudinal 19,[26][27][28] or cross-sectional design. 29 While surgical explants offer convenience and supply tissue without invasive biopsy procedures, women undergoing indicated surgery invariably have a host of medical comorbidities and concomitant medication use, which may affect study endpoints.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women

Thurman

Chandra

Yousefieh

et al. 2016

AIDS Research and Human Retroviruses

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The purpose of this study was to evaluate differences in vaginal immune cell populations, vaginal tissue gene expression, antimicrobial activity of the cervicovaginal (CV) lavage (CVL), vaginal flora, and p24 antigen production from CV tissues after ex vivo human immunodeficiency virus (HIV) infection between follicular (FOL) and luteal (LUT) phases of the menstrual cycle. CV tissue biopsies, CV secretions, and blood samples were obtained as part of two longitudinal clinical trials of healthy women (CONRAD D11-119 and A12-124 studies). Participants (n = 39) were HIV-seronegative women not using exogenous hormone supplementation, with normal menstrual cycles, who were screened to exclude sexually transmitted and reproductive tract infections. Serum levels of estradiol and progesterone were significantly higher in the LUT versus the FOL phase of the menstrual cycle. Controlling for race, reported contraceptive use/sexual practices, and clinical trial, we found no differences in vaginal tissue immune cell populations and activation status, transcriptomes, inhibition of HIV, herpes simplex virus type 2 and Escherichia coli by the CVL, vaginal pH or Nugent score, or production of p24 antigen after ex vivo infection by HIV-1 BaL between CV samples obtained in the FOL phase versus the LUT phase of the menstrual cycle. There were no significant correlations between serum estradiol and progesterone levels and CV endpoints. The hypothesis that the LUT phase of the menstrual cycle represents a more vulnerable stage for mucosal infection with HIV was not supported by data from samples obtained from the lower genital tract (ectocervix and vagina) from these two clinical trials.

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

Abstract: We provide evidence of elevated vaginal cytokine levels during menses, which appear to regulate vaginal and not plasma HIV shedding, suggesting that a menstrual cycle pattern exists for cytokine production in HIV-positive women impacting vaginal shedding of HIV.

Cited by 65 publications

References 24 publications

Vaginal IL-8 levels are positively associated with Candida albicans and inversely with lactobacilli in HIV-infected women

Vaginal IL-8 levels are positively associated with Candida albicans and inversely with lactobacilli in HIV-infected women

Fourteen-day safety and acceptability study of 6% cellulose sulfate gel: a randomized double-blind Phase I safety study

Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women

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