title: Safety analysis of the diaphragm in combination with lubricant or acidifying microbicide gels: effects on markers of inflammation and innate immunity in cervicovaginal fluid.
abstract: OBJECTIVE
  Diaphragms are being considered for use with vaginal microbicide gels to provide enhanced protection against sexually transmitted pathogens. The purpose of this study was to determine whether use of a diaphragm with microbicide or placebo gel causes cervicovaginal inflammation or perturbations in cervicovaginal immune defense.
  
  
  METHODS
  Eighty-one non-pregnant women were randomized into three groups and instructed to use Milex (CooperSurgical, Inc., Trumbull, CT, USA)diaphragms overnight for 14 days in combination with one of the two acid-buffering microbicide gels [ACIDFORM (Instead Inc., La Jolla, CA, USA) or BufferGel(trade mark) (BG; ReProtect Inc., Baltimore, Maryland)] or placebo gel (K-Y Jelly); Personal Products Inc., Raritan, NJ, USA). Cervicovaginal lavages (CVLs) were performed prior to study entry and on days 8 and 16. Nine soluble mediators of vaginal inflammation or immune defense were measured in CVLs by Bio-Plex or ELISA.
  
  
  RESULTS
  Use of diaphragms with placebo or microbicide gel was not associated with increased levels of inflammation markers. Concentrations of secretory leukocyte protease inhibitor (SLPI) were markedly reduced in the BG group.
  
  
  CONCLUSIONS
  Daily use of a diaphragm with placebo or acidifying microbicide gel did not cause cervicovaginal inflammation. However, diaphragm/BG use was associated with markedly reduced levels of SLPI, an important mediator of innate immune defense. Further studies are warranted to establish the safety of diaphragm/microbicide gel combinations.
authors.affiliation: Department of Obstetrics and Gynecology, Boston University School of Medicine, 670 Albany St., Suite 516, Boston, MA 02118, USA. deborah.anderson@BMC.org
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Anderson
authors.forename: D'Nyce L
authors.initials: DL
authors.lastname: Williams
authors.forename: Susan A
authors.initials: SA
authors.lastname: Ballagh
authors.forename: Kurt
authors.initials: K
authors.lastname: Barnhart
authors.forename: Mitchell D
authors.initials: MD
authors.lastname: Creinin
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Newman
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Bowman
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Politch
authors.forename: Ann C
authors.initials: AC
authors.lastname: Duerr
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Jamieson
mesh_terms: D000293:Adolescent; D000328:Adult; D000891:Anti-Infective Agents, Local / Q000009:adverse effects* / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D003274:Contraceptive Devices, Female; D016207:Cytokines / Q000032:analysis; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007249:Inflammation / Q000276:immunology*; D008875:Middle Aged; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000891:Anti-Infective Agents, Local; D015415:Biomarkers; D016207:Cytokines; D014622:Vaginal Creams, Foams, and Jellies