Pathogenesis of abnormal vaginal bacterial flora

OBJECTIVE: This study was undertaken to determine the relationships between microscopy findings on wet mounts, such as lactobacillary grade or vaginal leukocytosis, and results of vaginal culture, lactate and succinate conten t of the vagina, and levels of selected cytokines. STUDY DESIGN: In a population of 631 unselected women seeking treatment at an obstetrics and gynecology outpatient clinic, vaginal fluid was obtained by wooden Ayre spatula for wet mounting and pH measurement, by high vaginal swab for culture, and by standardized vaginal rinsing with 2 mL 0.9% sodiu m chloride solution for measurements of lactate, succinate, interleukin 1 b eta, interleukin 8, leukemia inhibitory factor, and interleukin 1 receptor antagonist concentrations. Lactate and succinate levels were measured by ga s-liquid chromatography and the cytokine concentrations were measured by sp ecific immunoassays. Both univariate analysis (Student t test, Welch test, chi(2) test, and Fisher exact test) and multivariate regression analysis (C ox analysis) were used. RESULTS: Increasing disturbance of the lactobacillary flora (lactobacillary grades I, IIa, IIb, and III) was highly correlated with the presence of Ga rdnerella vaginalis, Trichomonas vaginalis, enterococci, group B streptococ ci, and Escherichia coli. Vaginal pH and interleukin 8 and interleukin 1 be ta concentrations increased linearly with increasing lactobacillary grade, whereas lactate concentrations and the presence of epithelial cell lysis de creased. A similar pattern of associations with increasing leukocyte count was clear, but in addition there was an increase in leukemia inhibitory fac tor concentration. Multivariate analysis of vaginal leukocytosis, lactobaci llary grades, and the presence of positive Vaginal culture results showed t hat interleukin 1 beta concentration was most closely related to the lactob acillary grade, leukemia inhibitory factor concentration was most closely r elated to the lactobacillary grade and positive culture results, interleuki n 8 concentration was most closely related to positive culture results, and interleukin 1 receptor antagonist concentration was most closely related t o vaginal leukocytosis and positive culture results. The concentration rati o of interleukin 1 beta to interleukin 1 receptor antagonist remained stabl e, except when vaginal leukocytosis increased. In its most severe form, wit h >10 leukocytes per epithelial cell present, a decompensation of the vagin al flora with a collapse in interleukin 1 beta and interleukin 1 receptor a ntagonist concentrations was seen, but there was a concurrent sharp increas e in leukemia inhibitory factor concentration. This pattern was completely different from the course of the cytokine concentrations associated with a lactobacillary grade increase. CONCLUSION: Both disturbed lactobacillary grade and the presence of increas ing vaginal leukocytosis were correlated with lactobacillary substrate (lac tate) concentration, pH, and the concentrations of a variety of cytokines. There was a remarkably linear increase in these cytokines as either leukocy tosis or lactobacillary grade became more severe. In circumstances in which leukocytosis was extreme, however, interleukin 1 beta was no longer produc ed but leukemia inhibitory factor concentrations increased. We speculate th at in extreme inflammation the body tries to limit the damage that can be d one by exaggerated cytokine production.