Enhanced synthesis of proinflammatory cytokines by vulvar vestibular fibroblasts: implications for vulvar vestibulitis.
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.
Foster
David C
DC
Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. david_foster@urmc.rochester.edu
Piekarz
Katherine H
KH
Murant
Thomas I
TI
LaPoint
Randi
R
Haidaris
Constantine G
CG
Phipps
Richard P
RP
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*
D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D000521:alpha-MSH