Defective regulation of the proinflammatory immune response in women with vulvar vestibulitis syndrome

Am J Obstet Gynecol. 2002 Apr;186(4):696-700. doi: 10.1067/mob.2002.121869.

Abstract

Objective: The cause of vulvar vestibulitis syndrome is unknown. To determine a possible role for defective immune regulation in this chronic condition, proinflammatory and anti-inflammatory immune responses to the 70-kd heat shock protein and to lipopolysaccharide were compared in women with and without vulvar vestibulitis syndrome.

Study design: Whole blood cultures from 62 women with vulvar vestibulitis syndrome and 48 control subjects were incubated in the presence or absence of 5 microg/mL human recombinant 70-kd heat shock protein or 0.1 ng/mL lipopolysaccharide for 18 hours. The culture supernatants were then assayed for interleukin-1 beta and interleukin-1 receptor antagonist by enzyme-linked immunosorbent assay.

Results: Median levels of interleukin-1 beta were higher in response to heat shock protein in cultures from patients with vulvar vestibulitis syndrome (median, 1.07 ng/mL) as opposed to control subjects (median, 0.40 ng/mL; P =.006). Conversely, levels of interleukin-1 receptor antagonist were higher in response to heat shock protein in control subjects (median, 39.21 ng/mL) than in patients (median, 29.25 ng/mL; P =.009). In response to lipopolysaccharide, median levels of interleukin-1 beta were similar in patients (1.00 ng/mL) and control subjects (1.15 ng/mL); median interleukin-1 receptor antagonist concentrations were higher in control subjects (70.0 ng/mL) than in patients (44.3 ng/mL; P <.0001). The ratio of interleukin-1 receptor antagonist to interleukin-1 beta was higher in control subjects than in women with vulvar vestibulitis syndrome in response to both heat shock protein (P =.0002) and lipopolysaccharide (P =.01). In uninduced cultures, interleukin-1 receptor antagonist levels were also higher in control subjects (median, 1.60 ng/mL) than in patients with vulvar vestibulitis syndrome (median, 0.62 ng/mL; P <.0001).

Conclusion: A relative inability to down-regulate proinflammatory interleukin-1 beta activity by interleukin-1 receptor antagonist may contribute to the pathophysiologic features of vulvar vestibulitis syndrome.

MeSH terms

  • Cytokines / biosynthesis*
  • Cytokines / blood
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli
  • Female
  • HSP70 Heat-Shock Proteins / pharmacology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / analysis
  • Interleukin-1 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Sialoglycoproteins / analysis
  • Sialoglycoproteins / biosynthesis
  • Syndrome
  • Vulvitis / blood
  • Vulvitis / immunology*

Substances

  • Cytokines
  • HSP70 Heat-Shock Proteins
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Lipopolysaccharides
  • Sialoglycoproteins