Safety analysis of the diaphragm in combination with lubricant or acidifying microbicide gels: effects on markers of inflammation and innate immunity in cervicovaginal fluid.
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.
Anderson
Deborah J
DJ
Department of Obstetrics and Gynecology, Boston University School of Medicine, 670 Albany St., Suite 516, Boston, MA 02118, USA. deborah.anderson@BMC.org
Williams
D'Nyce L
DL
Ballagh
Susan A
SA
Barnhart
Kurt
K
Creinin
Mitchell D
MD
Newman
Daniel R
DR
Bowman
Frederick P
FP
Politch
Joseph A
JA
Duerr
Ann C
AC
Jamieson
Denise J
DJ
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
D000891:Anti-Infective Agents, Local; D015415:Biomarkers; D016207:Cytokines; D014622:Vaginal Creams, Foams, and Jellies