title: No increase in cervicovaginal proinflammatory cytokines after Carraguard use in a placebo-controlled randomized clinical trial.
abstract: BACKGROUND
  Assessment of cervicovaginal cytokine levels may be helpful to evaluate subclinical epithelial inflammation during safety evaluations of candidate microbicides.
  
  
  METHODS
  Fifty-five HIV-seronegative Thai women were enrolled in a safety trial of the candidate microbicide Carraguard and were randomized to use Carraguard or placebo gel before vaginal sex. Cervicovaginal lavages were collected at baseline and after 1 month of gel use; levels of interleukin (IL)-1beta, IL-6, IL-8, and secretory leukocyte protease inhibitor (SLPI) were measured using microwell plate-based enzyme immunoassays. Median levels were compared between the baseline and 1-month follow-up visits using paired t tests; the median change between groups was compared using Wilcoxon rank sum tests. Women were examined for the presence of genital findings; the association between genital findings and cytokine levels was studied.
  
  
  RESULTS
  No increase in levels of proinflammatory cytokines after use of Carraguard gel or placebo gel was observed during the study. The median change from the baseline to 1 month of follow-up was not significantly different between Carraguard and placebo groups (IL-1beta: -0.3 pg/mL vs. -3.93 pg/mL; P = 0.4, IL-6: -0.3 pg/mL vs. 0 pg/mL; P = 0.3, IL-8: -40.1 pg/mL vs. -53.2 pg/mL; P = 0.8, and SLPI: -26.5 pg/mL vs. 12.6 pg/mL; P = 0.07). Genital findings with intact epithelium were found in 16 (29%) women; these women tended to have somewhat higher IL-6 levels than those with normal epithelium (14.9 pg/mL vs. 8.8 pg/mL; P = 0.08).
  
  
  CONCLUSIONS
  We found no increase in proinflammatory cytokines after Carraguard and placebo gel use, suggesting that neither gel causes inflammation. Further studies to assess the role of cytokines in microbicide safety studies are warranted.
authors.affiliation: Thailand Ministry of Public Health--US Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand. lbollen@tuc.or.th
authors.forename: Liesbeth J M
authors.initials: LJ
authors.lastname: Bollen
authors.forename: Kelly
authors.initials: K
authors.lastname: Blanchard
authors.forename: Peter H
authors.initials: PH
authors.lastname: Kilmarx
authors.forename: Supaporn
authors.initials: S
authors.lastname: Chaikummao
authors.forename: Cathy
authors.initials: C
authors.lastname: Connolly
authors.forename: Punneporn
authors.initials: P
authors.lastname: Wasinrapee
authors.forename: Nucharee
authors.initials: N
authors.lastname: Srivirojana
authors.forename: Jullapong
authors.initials: J
authors.lastname: Achalapong
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Tappero
authors.forename: Janet M
authors.initials: JM
authors.lastname: McNicholl
mesh_terms: D000328:Adult; D000891:Anti-Infective Agents, Local / Q000633:toxicity*; D002584:Cervix Uteri / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D010919:Placebos / Q000008:administration & dosage; D012749:Sexually Transmitted Diseases / Q000517:prevention & control; D013785:Thailand; D014621:Vagina / Q000473:pathology*; D014622:Vaginal Creams, Foams, and Jellies / Q000633:toxicity*; D044364:Vaginal Douching
chemical_list: D000891:Anti-Infective Agents, Local; D016207:Cytokines; D010919:Placebos; D014622:Vaginal Creams, Foams, and Jellies