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


METHODS
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).


CONCLUSIONS
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.
Gerber
Stefan
S
Department of Obstetrics and Gynecology, Division of Immunology and Infectious Diseases, Weill Medical College of Cornell University, New York, NY 10021, USA.
Bongiovanni
Ann Marie
AM
Ledger
William J
WJ
Witkin
Steven S
SS
D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000032:analysis / Q000096:biosynthesis; D013577:Syndrome; D014847:Vulvitis / Q000097:blood / Q000276:immunology*
D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012795:Sialoglycoproteins