title: Increased CCL2 expression and macrophage/monocyte migration during microbicide-induced vaginal irritation.
abstract: Despite availability of successful prevention strategies, HIV continues to spread at alarming rates, especially among women in developing countries. Vaginal microbicides offer a promising approach for blocking transmission of HIV when condom use cannot be negotiated with male partners. A major problem in the development of vaginal microbicides is chemically induced vaginal irritation, which can enhance the risk of HIV transmission. Evaluation of vaginal irritation prior to clinical trials typically uses an expensive and animal-intensive rabbit vaginal irritation model, which could be supplemented by measuring additional inflammatory biomarkers. We studied several immunological parameters as potential biomarkers of vaginal irritation, using the spermicides nonoxynol-9 and benzalkonium chloride as test microbicides. We measured amounts of cytokines, as well as inflammatory cells, in vaginal tissue lysates and on the vaginal surface. We observed that treatment with the selected microbicides increases quantities of the inflammatory cytokines interleukin-1beta, CXCL8, and CCL2 in the vaginal tissue parenchyma, and of CCL2 on the vaginal surface. This observation was correlated with increases in macrophages in the vaginal parenchyma. We suggest that measurements of CCL2 and macrophages can serve as new inflammatory biomarkers to evaluate the safety of promising novel microbicides for prevention of HIV.
authors.affiliation: Biosciences Division, SRI International, Menlo Park, CA 94025, USA. carsten.alt@sri.com
authors.forename: Carsten
authors.initials: C
authors.lastname: Alt
authors.forename: Travis
authors.initials: T
authors.lastname: Harrison
authors.forename: Linda
authors.initials: L
authors.lastname: Dousman
authors.forename: Nahoko
authors.initials: N
authors.lastname: Fujita
authors.forename: Ken
authors.initials: K
authors.lastname: Shew
authors.forename: Thanh-Thuy
authors.initials: TT
authors.lastname: Tran
authors.forename: Sara
authors.initials: S
authors.lastname: Shayesteh
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsukawa
authors.forename: Jon
authors.initials: J
authors.lastname: Mirsalis
authors.forename: Annalisa
authors.initials: A
authors.lastname: D'Andrea
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds / Q000009:adverse effects*; D015415:Biomarkers; D002465:Cell Movement / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D017137:Nonoxynol / Q000009:adverse effects*; D011817:Rabbits; D013501:Surface-Active Agents / Q000009:adverse effects*; D014621:Vagina / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
chemical_list: D001548:Benzalkonium Compounds; D015415:Biomarkers; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D016209:Interleukin-8; D013501:Surface-Active Agents; D017137:Nonoxynol