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-1β, 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.
Keywords: Cytokine, chemokine, HIV, AIDS, sexually transmitted disease, biomarker
Current HIV Research
Title: Increased CCL2 Expression and Macrophage/Monocyte Migration During Microbicide-Induced Vaginal Irritation
Volume: 7 Issue: 6
Author(s): Carsten Alt, Travis Harrison, Linda Dousman, Nahoko Fujita, Ken Shew, Thanh-Thuy Tran, Sara Shayesteh, Akihiro Matsukawa, Jon Mirsalis and Annalisa D'Andrea
Affiliation:
Keywords: Cytokine, chemokine, HIV, AIDS, sexually transmitted disease, biomarker
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-1β, 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.
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Cite this article as:
Alt Carsten, Harrison Travis, Dousman Linda, Fujita Nahoko, Shew Ken, Tran Thanh-Thuy, Shayesteh Sara, Matsukawa Akihiro, Mirsalis Jon and D'Andrea Annalisa, Increased CCL2 Expression and Macrophage/Monocyte Migration During Microbicide-Induced Vaginal Irritation, Current HIV Research 2009; 7 (6) . https://dx.doi.org/10.2174/157016209789973682
DOI https://dx.doi.org/10.2174/157016209789973682 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
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Management of HIV: Management of HIV: old challenges and new needs
The aim of this thematic issue is to provide the most recent updates regarding the effective management of HIV infection. Antiretroviral therapy (ART) has significantly decreased HIV-related mortality, leading to an enhancement in the quality of life and life expectancy for people living with HIV (PLWH). Despite the numerous advancements ...read more
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