Evaluation of the lymphocyte trafficking drug FTY720 in vaginal tissues

J Med Primatol. 2013 Apr;42(2):89-100. doi: 10.1111/jmp.12033. Epub 2013 Jan 12.

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 (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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Intravaginal
  • Administration, Intravenous
  • Animals
  • Anti-Infective Agents
  • Cervix Uteri / chemistry
  • Cervix Uteri / drug effects
  • Cervix Uteri / immunology
  • Drug Evaluation, Preclinical
  • Female
  • Fingolimod Hydrochloride
  • HIV Infections / prevention & control
  • Immunosuppressive Agents
  • Interleukin 1 Receptor Antagonist Protein / analysis
  • Interleukin-8 / analysis
  • Lymphocyte Count*
  • Macaca nemestrina*
  • Mucous Membrane / chemistry
  • Mucous Membrane / drug effects
  • Mucous Membrane / immunology
  • Pilot Projects
  • Placebos
  • Propylene Glycols / administration & dosage*
  • Propylene Glycols / adverse effects
  • Sphingosine / administration & dosage
  • Sphingosine / adverse effects
  • Sphingosine / analogs & derivatives*
  • Vagina / chemistry
  • Vagina / drug effects*
  • Vagina / immunology*
  • Vaginal Creams, Foams, and Jellies

Substances

  • Anti-Infective Agents
  • Immunosuppressive Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-8
  • Placebos
  • Propylene Glycols
  • Vaginal Creams, Foams, and Jellies
  • Fingolimod Hydrochloride
  • Sphingosine