interleukin-8 and Candidiasis--Vulvovaginal

Secretory aspartyl proteinases (Saps) of Candida albicans are key virulence traits which cause inflammasome-dependent, aseptic inflammation in a mouse model of vaginitis. In this paper, neutrophil migration in response to Sap2, Sap6 and chemo-attractive products released from Sap-treated vaginal epithelium was measured in vitro, ex vivo and in vivo. Our results show that Sap2 and Sap6 induce neutrophil migration and production of potent chemoattractive chemokines such as IL-8 and MIP-2 by vaginal epithelial cells. Our data suggest that at least part of MIP-2 production depends upon IL-1β activity. The vaginal fluid of Candida-infected mice contained a heat-labile inhibitor of neutrophil candidacidal activity that was absent from the vaginal fluid of Sap-treated mice. Overall, our data provide additional information on the capacity of C. albicans Saps to cause aseptic vaginal inflammation and highlight the potential role of some chemokines released from vaginal epithelial cells in this phenomenon.

Topics: Animals; Aspartic Acid Endopeptidases; Candida albicans; Candidiasis, Vulvovaginal; Chemokine CXCL2; Chemotaxis, Leukocyte; Disease Models, Animal; Epithelial Cells; Female; Fungal Proteins; Humans; Interleukin-8; Mice; Neutrophils; Vagina

Vulvovaginal candidiasis (VVC) is among the most prevalent vaginal diseases. Candida albicans is still the most prevalent species associated with this pathology, however, the prevalence of other Candida species, such as C. glabrata, is increasing. The pathogenesis of these infections has been intensely studied, nevertheless, no consensus has been reached on the pathogenicity of VVC. In addition, inappropriate treatment or the presence of resistant strains can lead to RVVC (vulvovaginal candidiasis recurrent). Immunomodulation therapy studies have become increasingly promising, including with the β-glucans. Thus, in the present study, we evaluated microbicidal activity, phagocytosis, intracellular oxidant species production, oxygen consumption, myeloperoxidase (MPO) activity, and the release of tumor necrosis factor α (TNF-α), interleukin-8 (IL-8), IL-1β, and IL-1Ra in neutrophils previously treated or not with β-glucan. In all of the assays, human neutrophils were challenged with C. albicans and C. glabrata isolated from vulvovaginal candidiasis. β-glucan significantly increased oxidant species production, suggesting that β-glucan may be an efficient immunomodulator that triggers an increase in the microbicidal response of neutrophils for both of the species isolated from vulvovaginal candidiasis. The effects of β-glucan appeared to be mainly related to the activation of reactive oxygen species and modulation of cytokine release.

Topics: beta-Glucans; Candida albicans; Candida glabrata; Candidiasis, Vulvovaginal; Female; Humans; Hypochlorous Acid; Interleukin-1beta; Interleukin-8; Intracellular Space; Neutrophils; Oxygen Consumption; Peroxidase; Phagocytosis; Reactive Oxygen Species; Recurrence; Sulfhydryl Compounds; Tumor Necrosis Factor-alpha

To determine the concentration of certain cytokines and immunoglobulin (Ig) E in the vaginal lavage fluid (VLF) of women with vulvovaginal candidiasis (VVC).. Cytokin and IgE concentrations were measured in the VLF of women with VVC; women free of any genital infections acted as controls.. The VLF concentrations of interleukin (IL)-2, IL-8, and interferon (INF)-gamma were higher among women with VVC than in the control group; women with severe VVC had a higher VLF concentration of IL-4 than those with mild to moderate VVC; women with cured VVC had a higher VLF concentration of IL-13 than did controls; and women with VVC or cured VVC had a higher VLF concentration of IgE than did controls (P<0.05 for all).. Both helper T cells type 1 and innate response cytokines were shown to play a dominant role in the pathogenesis of VVC. This allergic vaginal response in women with VVC suggests that the form of treatment for VVC should be reconsidered.

Topics: Candidiasis, Vulvovaginal; Cytokines; Female; Humans; Immunoglobulin E; Interferon-gamma; Interleukin-13; Interleukin-2; Interleukin-4; Interleukin-8; Severity of Illness Index; Vagina; Vaginal Douching

The purpose of the study was to measure and compare concentrations of IFN-gamma, IL-8, IL-10 and IL-12 in cervical fluids of pregnant women with normal and pathologic microscopic findings of vaginal wet mount.. Vaginal samples were obtained from 100 pregnant women (22-32 weeks of gestation) without signs and symptoms of preterm labour (PTL), selected on the basis of the microscopic examination of vaginal wet mounts. Cytokine (IFN-gamma, IL-8, IL-10 and IL-12) concentrations were measured in cervical fluids by an enzyme-linked immunosorbent assay.. The cytokines were found in cervical fluids of the majority of pregnant women, with IFN-gamma and IL-8 detected in all samples. Concentrations of IL-8 were significantly higher in pregnant women with pathologic findings on vaginal wet mount, including elevated polymorphonuclear (PMN) cell counts.. A significant correlation between microscopic findings and cervical fluid IL-8 concentrations may make vaginal wet mount microscopy a useful tool for identification of patients with cervicovaginal inflammation, which is considered a risk factor for spontaneous preterm delivery.

Topics: Bodily Secretions; Candidiasis, Vulvovaginal; Cervix Uteri; Female; Humans; Interferon-gamma; Interleukin-8; Leukocyte Count; Neutrophils; Pregnancy; Vagina; Vaginosis, Bacterial

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

Topics: Adult; alpha-MSH; Biopsy, Needle; Candida albicans; Candidiasis, Vulvovaginal; Case-Control Studies; Cells, Cultured; Cytokines; Female; Fibroblasts; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Middle Aged; Probability; Reference Values; Sampling Studies; Sensitivity and Specificity; Statistics, Nonparametric; Vulvitis