Local immune responsiveness following intravaginal challenge with Candida antigen in adult women at different stages of the menstrual cycle

Recurrent vulvovaginal candidiasis ( RVVC) is a significant problem in women of childbearing age and is most often caused by Candida albicans that asymptomatically colonizes mucosal tissues. Although some form of local immune dysfunction is postulated to precipitate bouts of RVVC, the normal protective vaginal host response to C. albicans is poorly understood. In an effort to stimulate the natural adaptive response to yeast in healthy women without a history of VVC, commercial Candida skin test antigen was introduced intravaginally and changes in cytokines/ immunomodulators were monitored in vaginal lavage fluid pre- and post- antigen challenge. In an earlier pilot study using small numbers of women without controlling for stages of the menstrual cycle, we reported elevated cytokines in vaginal secretions of antigen challenged women. The present study, however, that employed a similar design in a large number of women during each stage of the menstrual cycle showed no evidence of local immune stimulation, including changes in Th and proinflammatory cytokines, IgE, histamine, and prostaglandin, despite a natural modulation of vaginal cytokines over the course of the menstrual cycle. Taken together, these results suggest that either some form of vaginal immunoregulation/ tolerance is evident in response to yeast or that more advanced clinical designs are required to detect the normal protective vaginal response to C. albicans.