title: Enhanced synthesis of proinflammatory cytokines by vulvar vestibular fibroblasts: implications for vulvar vestibulitis.
abstract: OBJECTIVE
  The objective of the study was to determine whether vestibular fibroblasts from vulvar vestibulitis (VVS) patients produce higher proinflammatory cytokine levels when provoked with Candida albicans (yeast) and alpha-melanocyte-stimulating hormone (alpha-MSH) in vitro.
  
  
  METHODS
  Twenty anatomically defined fibroblast strains from patients and age-matched controls were stimulated with 5 regimens: no stimulus, alpha-MSH, heat-killed yeast, alpha-MSH plus yeast, and interleukin (IL)-1beta. Supernatant products included the following: granulocyte macrophage colony-stimulating factor, interferon-gamma, IL-10, IL-12, IL-1beta, IL-2, IL-4, IL-6, IL-8, and tumor necrosis factor-alpha were assayed.
  
  
  RESULTS
  Coincubation with alpha-MSH plus yeast significantly increased IL-6 (3-fold) and IL-8 (greater than 40-fold) production in patients and controls. Vestibular fibroblast exceeded external vulvar fibroblast production of IL-1beta, IL-6, and IL-8 following yeast alone and alpha-MSH plus yeast stimuli in patients and controls. Substratified by anatomic origin, vestibular fibroblasts from VVS patients produced the highest relative levels of IL-1beta, IL-6, and IL-8 at baseline and following the yeast-alone regimen.
  
  
  CONCLUSIONS
  Localized pain of VVS may results from regionally elevated cytokines produced by vulvar vestibule-specific fibroblasts.
authors.affiliation: Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. david_foster@urmc.rochester.edu
authors.forename: David C
authors.initials: DC
authors.lastname: Foster
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Piekarz
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Murant
authors.forename: Randi
authors.initials: R
authors.lastname: LaPoint
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Haidaris
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D002176:Candida albicans; D002181:Candidiasis, Vulvovaginal / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014847:Vulvitis / Q000378:metabolism* / Q000473:pathology; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D000521:alpha-MSH