The molecular basis of nonoxynol-9-induced vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 transmission

Topical microbicides are being sought to prevent sexually transmitted disea ses by inactivating pathogens while preserving or enhancing the natural muc osal barrier. Serious public health concerns were raised by a recent phase 3 clinical trial that showed that nonoxynol-9 (N-9), a leading microbicide candidate widely used as an over-the-counter spermicide, may actually incre ase human immunodeficiency virus type 1 (HIV-1) transmission. The present s tudy links N-9-induced vaginal inflammation to increased risk of HIV-1 infe ction. Analysis of molecular and cellular components in cervicovaginal secr etions, as well as results from in vitro activation of cervicovaginal epith elial cells and U1/HIV promonocytic cells, showed that multiple N-9 use can promote HIV-1 transmission through interleukin-1-mediated NF-kappaB activa tion, which leads to chemokine-induced recruitment of HIV-1 host cells and increased HIV-1 replication in infected cells. Furthermore, this study iden tifies in vitro and in vivo model systems for monitoring undesirable proinf lammatory effects of microbicides and other vaginal products.