Evaluation of the lymphocyte trafficking drug FTY720 in vaginal tissues

淋巴细胞运输药物 FTY720 在阴道组织中的评估

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作者:Ai Tsuiki, Wei Luo, Tara Henning, Sundaram Vishwanathan, Chuong Dinh, Debra Adams, Elizabeth Sweeney, James Mitchell, Shannon Bachman, Prachi Sharma, Nathaniel Powell, Michael Hendry, Janet McNicholl, Ellen Kersh

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.

Conclusions

This study introduces FTY720 as an immunomodulatory agent for the vaginal mucosa, compares topical effects to those of i.v. administration, and provides the basis for future studies involving FTY720 for HIV prevention.

Methods

Five female pigtail macaques received topical vaginal gel FTY720 (n = 2), intravenous (i.v.) 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 i.v. FTY720 effects.

Results

Topical and i.v. 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 i.v. administration, and provides the basis for future studies involving FTY720 for HIV prevention.

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