Infiltration of white blood cells (WBC) into the vagina following vaginal application of Commercial Nonoxynol-9 Preparations

Abstract

Nonoxynol-9 (N-9) is commonly used as a spermicidal agent in vaginal contraceptives and is being evaluated for use in topical microbicide formulations. However, frequent use of N-9 may cause vaginal irritation and erosions. We used a mouse model to explore the basis for cytotoxic effects of N-9 by examining the influence of N-9 application on infiltration of inflammatory cells into the vagina. A naturally occurring population of WBC comprised predominately of neutrophils (> 98%) was detected in the vaginae of control mice. By four hours after vaginal N-9 application the number of viable WBC in the vaginae of N-9 treated mice was approximately 4-fold greater than in placebo-treated controls. The number of viable WBC in the inflammatory infiltrate of N-9 treated mice continued increasing and was significantly higher by 8 hours after application compared to placebo-treated controls (p < 0.05). The vaginal inflammatory response began resolving by 24 hours after a single N-9 treatment as measured by a decrease in total number of vaginal WBC. Application of microbicide preparations containing 4% N-9 resulted in greater numbers of infiltrating WBC than did preparations containing lower N-9 concentrations. Although increased numbers of neutrophils were detected in the vaginal infiltrate of N-9 treated mice, up to 50% of the infiltrating WBC were identified as macrophages by differential staining of lavage cells. No significant increase in the number of lymphocytes was detected by vaginal lavage following N-9 treatment. These data suggest that application of N-9 resulted in rapid infiltration of WBC onto the surface of the vaginal mucosa. It is possible that the release of proinflammatory cytokines and cytotoxic molecules by these infiltrating cells may be involved in initiating and executing the non-specific tissue damage resulting from repeated N-9 use. Further, because macrophages serve as a target for infection by the human immunodeficiency virus (HIV) and because of the potential for improper use of microbicides, the infiltration of macrophages into the vagina following N-9 application has implications regarding spread of HIV infection.