Enhanced synthesis of proinflammatory cytokines by vulvar vestibular fibroblasts: implications for vulvar vestibulitis

Am J Obstet Gynecol. 2007 Apr;196(4):346.e1-8. doi: 10.1016/j.ajog.2006.12.038.


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.

Study design: 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.

Conclusion: Localized pain of VVS may results from regionally elevated cytokines produced by vulvar vestibule-specific fibroblasts.

Publication types

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

MeSH terms

  • Adult
  • Biopsy, Needle
  • Candida albicans*
  • Candidiasis, Vulvovaginal / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Female
  • Fibroblasts / metabolism*
  • Humans
  • Interleukin-1beta / biosynthesis
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Middle Aged
  • Probability
  • Reference Values
  • Sampling Studies
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Vulvitis / metabolism*
  • Vulvitis / pathology
  • alpha-MSH / pharmacology*


  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • alpha-MSH