Evaluation of the lymphocyte trafficking drug FTY720 in vaginal tissues

• Type of Material: Article
• Authors: Ai Tsuiki, CDC, Atlanta; Wei Luo, CDC, Atlanta; Tara Henning, CDC, Atlanta; Sundaram Vishwanathan, CDC, Atlanta; Chuong Dinh, Total Solutions, Atlanta; Debra Adams, CDC, Atlanta; Elizabeth Sweeney, CDC, Atlanta; James Mitchell, CDC, Atlanta; Shannon Bachman, CDC, Atlanta; Prachi Sharma, Emory University; Nathaniel Powell, CDC, Atlanta; R. Michael Hendry, CDC, Atlanta; Janet McNicholl, CDC, Atlanta; Ellen Kersh, CDC, Atlanta
• Language: English
• Date: 2013-04-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1111/jmp.12033
• Title of Journal or Parent Work: Journal of Medical Primatology
• ISSN: 0047-2565
• Volume: 42
• Issue: 2
• Start Page: 89
• End Page: 100
• Grant/Funding Information: This work was partially supported by Interagency Agreement Y1-AI-0681-02 between CDC and NIH.; A.T. was funded by Division of Scientific Resources.; This work was funded by the Centers for Disease Control and Prevention.
• Keywords: HIV-1 INFECTION; CELLS; IN-VITRO; non-human primates; Life Sciences & Biomedicine; SEX WORKERS; genital; Veterinary Sciences; HUMAN-IMMUNODEFICIENCY-VIRUS; PREVENTION; MULTIPLE-SCLEROSIS; WOMEN; Science & Technology; Zoology; HIV; TRANSMISSION; ACTIVATION; topical gel
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Immunology

Abstract

Background: FTY720 is an immunomodulatory agent that reduces lymphocytes in peripheral tissues and circulation. Such agents may be effective as vaginal microbicides for HIV prevention. Systemic or vaginal application of FTY720 may reduce lymphocyte concentrations in genital tissues, reducing HIV target cell numbers. Methods: Five female pigtail macaques received topical vaginal gel FTY720 (n = 2), intravenous (IV) FTY720 (n = 2), or placebo gel (n = 1) in this pilot study. Circulating and mucosal lymphocytes and genital mucosa, cytokines, and tissue histology were analyzed to document topical and IV FTY720 effects. Results: Topical and IV FTY720 appeared to decrease the levels of cervicovaginal IL-8, IL-1ra, and genital inflammatory cells. Small sample size precluded statistical analysis. Topical administration had no overt adverse effects. Conclusions: This study introduces FTY720 as an immunomodulatory agent for the vaginal mucosa, compares topical effects to those of IV administration, and provides the basis for future studies involving FTY720 for HIV prevention.