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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
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
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Transdermal Delivery of 5-Fluorouracil for Induced Ehrlich Ascites Carcinoma Tumor in Balb/c Mice and Pharmacokinetic Study
Recent Patents on Anti-Cancer Drug Discovery Prognostic Relevance of Metabolic Approach in Patients with Heart Failure
Current Pharmaceutical Design Glucose Blood Levels as a Therapeutic Target in Acute Ischaemic Stroke Setting
Current Topics in Medicinal Chemistry Tanshinone IIA Protects Hippocampal Neuronal Cells from Reactive Oxygen Species Through Changes in Autophagy and Activation of Phosphatidylinositol 3-Kinase, Protein Kinas B, and Mechanistic Target of Rapamycin Pathways
Current Neurovascular Research Low Dose of Anisodine Hydrobromide Induced Neuroprotective Effects in Chronic Cerebral Hypoperfusion Rats
CNS & Neurological Disorders - Drug Targets Renin-Angiotensin-Aldosterone System: A Current Drug Target for the Management of Neuropathic Pain
Current Drug Targets Pharmacological Investigation and Unraveling Mechanism of Action of Jasminum sambac Flowers for Predicated Treatment of Alzheimer’s Disease
Current Nutrition & Food Science Complement and Microglia in the Neuropathogenesis of HIV Infection: Pro- and Anti-Inflammatory Aspects
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cytokine and Nitric Oxide Production Following Severe Envenomation
Current Drug Targets - Inflammation & Allergy Contribution of Glucocorticoids and Glucocorticoid Receptors to the Regulation of Neurodegenerative Processes
CNS & Neurological Disorders - Drug Targets Local Treatment for Lymphoid Malignancies of the Eye
Anti-Cancer Agents in Medicinal Chemistry Mucopolysaccharidosis Type IVA (Morquio A Disease): Clinical Review and Current Treatment: A Special Review
Current Pharmaceutical Biotechnology Mechanisms of Drug Resistance to Vascular Endothelial Growth Factor (VEGF) Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Gene Therapy in In Vivo Isolated Perfusion Models
Current Gene Therapy Angiogenesis Inhibitors: Implications for Combination with Conventional Therapies
Current Pharmaceutical Design Lithium and its Neuroprotective and Neurotrophic Effects: Potential Treatment for Post-Ischemic Stroke Sequelae
Current Drug Targets Current Status and Future Directions of Multimodality Therapy for Non- Small Cell Lung Cancer of the Superior Sulcus
Current Cancer Therapy Reviews Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair
CNS & Neurological Disorders - Drug Targets Potential Therapeutic Strategies of Regenerative Medicine for Renal Failure
Current Stem Cell Research & Therapy Glioma Therapy: A Novel Insight in the Immunotherapeutic Regime with T11TS/SLFA-3
Central Nervous System Agents in Medicinal Chemistry