Abstracts (complete list) - Wissenschaft Online

Carsten Alt, Travis Harrison, Akihiro Matsukawa, Charles Litterst, Jon Mirsalis, Annalisa
D'Andrea
Vaginal cytokine production as a biomarker for the safety
evaluation of microbicide-induced vaginal irritation
Vaginal microbicides may help to reduce the risk of infection with HIV or other sexually
transmitted diseases. For safety evaluation of novel vaginal microbicides, vaginal
irritation is generally assessed in rabbits by histopathologic analysis of the gastrouterine
organs after 10 days of treatment. This evaluation requires the sacrifice of the animals.
Minimally invasive approaches to measure the vaginal irritation caused by novel
microbicides would offer a more desirable alternative.
We measured the vaginal irritation caused by the spermicides benzalkonium chloride
(BZK) and nonoxynol-9 (N-9). We assessed not only the histopathological changes, but
also: (a) the cytokine amounts in vaginal tissue lysates and in cotton swab samples
collected from the vaginal surface, and (b) the inflammatory cells in cytobrush samples
collected from the vaginal surface.
After 6 days of treatment with N-9, a significant increase in histopathological changes
was observed. This effect was transient, being no longer detectable after 10 days of
treatment with N-9. Simultaneously processed vaginal tissues contained significantly
increased amounts of IL-8 and IL-1β, but only after 10 days of treatment with BZK.
Swab samples from the vaginal surface contained significantly elevated levels of MCP-1,
IL-8, and IL-1β, in some cases as early as 3 days after treatment began. Increased
numbers of inflammatory cells were detectable, possibly attracted by increased
amounts of the inflammatory chemokines MCP-1 and IL-8 on the vaginal surface.
These results suggest that measurement of IL-8, IL-1β, MCP-1, and inflammatory cells
on the vaginal surface may offer a noninvasive method to assist in developing novel
vaginal microbicides.