interleukin-8 and Vaginosis--Bacterial

The aim of this study was to evaluate the rise of the levels of proinflammatory cytokines - IL-1alpha, IL-1beta, IL-6 and IL-8 in vagina of women with bacterial vaginosis (BV) and if there is any relationship between this levels. One hundred and twenty females between 22nd and 36th week of pregnancy were enrolled in the study. According to the bacterial flora of cervico-vaginal fluid evaluated by Gram stain, all women were divided into three groups. Group I (53 females; 44.2%)--normal bacterial flora, group II (35 females; 29.2%)--intermediate flora, and group with BV (32 females; 26.6%). The level of IL-1b in women with BV was over twelve times higher than in women from I group (131.35 and 10.6 pg/mL respectively). The next was the level of IL-1alpha--about seven times higher (128.45 vs 19.1 pg/mL) and the levels of IL-6 and IL-8, which were 1.7 times higher (16.2 vs 9.7 pg/mL and 656.7 vs 375.3 pg/mL respectively). Except for IL-6 these differences of levels were statistically significant (p<0.05). The levels of IL-1beta in group of women with BV correlated strongly with levels of IL-1alpha (r=0.72; p<0.0001) and weakly with levels of IL-6 (r=0.31; p=0.017). The correlation coefficient between levels of IL-6 and IL-8 rose gradually in II and BV group and reached levels r=0.575; p=0.0014 and r=0.67; p=0.0009 respectively. Our findings show that in vagina of women with BV the levels of proinflammatory cytokines rise, and that the rise of levels is in certain cases correlated.

Topics: Adult; Body Fluids; Cervix Mucus; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Pregnancy; Pregnancy Complications, Infectious; Vagina; Vaginosis, Bacterial

To compare the efficacy of oral versus vaginal metronidazole treatment in pregnant women with bacterial vaginosis, and to compare cytokine profiles (interleukin-1beta, -6, and -8) in the cervical secretions of these women before and after treatment.. Pregnant women with bacterial vaginosis diagnosed both by Gram stain and clinical criteria were randomized to receive oral (n=52) or vaginal (n=50) metronidazole therapy. Cervical specimens for cytokine analysis and vaginal fluid for evaluation of bacterial vaginosis were obtained at baseline and 4 weeks after treatment.. There was no significant difference in therapeutic cure rates (defined as a Gram stain score of 0-3 and the absence of all four clinical signs of bacterial vaginosis) between the two groups (71% and 70% for the oral and vaginal groups, respectively, P=1.0). Cervical levels of interleukin-1beta, -6, and -8 were significantly lower after treatment among the 72 women cured of bacterial vaginosis (P<.001, P=.001, and P=.02, respectively) but not among women who failed to respond to therapy. For interleukin-1beta and -6, a significant decrease in cytokine level was observed in both the oral and vaginal treatment groups.. One week of oral metronidazole and 5 days of intravaginal metronidazole are equally efficacious for treatment of bacterial vaginosis during pregnancy. The decrease in cervical interleukin-1beta, -6, and -8 levels among women who established a normal flora after treatment but not among those with persistent bacterial vaginosis suggests a direct linkage between vaginal flora abnormalities and elevated cervical levels of interleukin-1beta, -6, and -8.

Topics: Administration, Intravaginal; Administration, Oral; Adolescent; Adult; Cytokines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gestational Age; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Metronidazole; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Probability; Reference Values; Severity of Illness Index; Treatment Outcome; Vaginosis, Bacterial

The vaginal microbiome includes diverse microbiota dominated by Lactobacillus [L.] spp. that protect against infections, modulate inflammation, and regulate vaginal homeostasis. Because it is challenging to incorporate vaginal microbiota into in vitro models, including organ-on-a-chip systems, we assessed microbial metabolites as reliable proxies in addition to traditional vaginal epithelial cultures (VECs). Human immortalized VECs cultured on transwells with an air-liquid interface generated stratified cell layers colonized by transplanted healthy microbiomes (L. jensenii- or L. crispatus-dominant) or a community representing bacterial vaginosis (BV). After 48-h, a qPCR array confirmed the expected donor community profiles. Pooled apical and basal supernatants were subjected to metabolomic analysis (untargeted mass spectrometry) followed by ingenuity pathways analysis (IPA). To determine the bacterial metabolites' ability to recreate the vaginal microenvironment in vitro, pooled bacteria-free metabolites were added to traditional VEC cultures. Cell morphology, viability, and cytokine production were assessed. IPA analysis of metabolites from colonized samples contained fatty acids, nucleic acids, and sugar acids that were associated with signaling networks that contribute to secondary metabolism, anti-fungal, and anti-inflammatory functions indicative of a healthy vaginal microbiome compared to sterile VEC transwell metabolites. Pooled metabolites did not affect cell morphology or induce cell death (∼5.5%) of VEC cultures (n = 3) after 72-h. However, metabolites created an anti-inflammatory milieu by increasing IL-10 production (p = .06, T-test) and significantly suppressing pro-inflammatory IL-6 (p = .0001), IL-8 (p = .009), and TNFα (p = .0007) compared to naïve VEC cultures. BV VEC conditioned-medium did not affect cell morphology nor viability; however, it induced a pro-inflammatory environment by elevating levels of IL-6 (p = .023), IL-8 (p = .031), and TNFα (p = .021) when compared to L.-dominate microbiome-conditioned medium. VEC transwells provide a suitable ex vivo system to support the production of bacterial metabolites consistent with the vaginal milieu allowing subsequent in vitro studies with enhanced accuracy and utility.

Topics: Anti-Inflammatory Agents; Bacteria; Female; Humans; Interleukin-6; Interleukin-8; Lactobacillus; Microbiota; Tumor Necrosis Factor-alpha; Vagina; Vaginosis, Bacterial

Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria, such as Gardnerella vaginalis, and low levels of "healthy" lactobacilli leads to bacterial vaginosis (BV), usually associated with a low-grade inflammatory process. Despite appropriate antibiotic treatment,

Topics: Anti-Bacterial Agents; beta-Defensins; Chemokines; Cytokines; Female; Gardnerella vaginalis; Humans; Interleukin-8; Lacticaseibacillus rhamnosus; Secretory Leukocyte Peptidase Inhibitor; Vagina; Vaginosis, Bacterial

We studied the effects of IL-1β, IL-8, TNFα, and prostaglandin E2α in concentrations typically observed in health and during inflammation on the growth of vaginal microbiota and its resistance to factors inhibiting the synthesis of proteins, nucleic acids, and peptidoglycans. An increase in the cytokine levels, characteristic of inflammation, inhibits the growth of Lactobacillus population and improves its resistance to adverse factors. The growth of the population of opportunistic microorganisms (S. aureus, E. coli) is stimulated under these conditions, while their resistance to adverse factors decreases. Hence, it seems that the cytokines regulate the behavior of the host cells and of its bacterial symbionts.

Topics: Body Fluids; Case-Control Studies; Dinoprostone; Drug Resistance, Bacterial; Escherichia coli; Female; Host-Pathogen Interactions; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-8; Lactobacillus; Microbiota; Staphylococcus aureus; Tumor Necrosis Factor-alpha; Vagina; Vaginosis, Bacterial

It was shown that IL-1β, IL-8, and IL-6 in concentrations similar to those in the vagina of healthy women stimulated the growth of normal microflora (Lactobacillus spp.) and suppressed the growth and biofilm production by S. aureus and E. coli. On the contrary, these cytokines in higher concentrations typical of vaginal dysbiosis suppressed normal microflora and stimulated the growth of opportunistic microorganisms. TGF-β1 in both doses produced a stimulating effects on study vaginal microsymbionts. It is hypothesized that pro-inflammatory cytokines serve as the molecules of interspecies communication coordinating the interactions of all components of the vaginal symbiotic system.

Topics: Adult; Corynebacterium; Escherichia coli; Female; Gene Expression; Host-Pathogen Interactions; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Lactobacillus; Microbial Sensitivity Tests; Microbiota; Staphylococcus aureus; Transforming Growth Factor beta1; Vagina; Vaginosis, Bacterial

Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health.. To investigate host-vaginal microbiota interactions and the impact on immune barrier function, we colonized 3-dimensional (3-D) human vaginal epithelial cells with 2 predominant species of vaginal microbiota (Lactobacillus iners and Lactobacillus crispatus) or 2 prevalent bacteria associated with bacterial vaginosis (Atopobium vaginae and Prevotella bivia).. Colonization of 3-D vaginal epithelial cell aggregates with vaginal microbiota was observed with direct attachment to host cell surface with no cytotoxicity. A. vaginae infection yielded increased expression membrane-associated mucins and evoked a robust proinflammatory, immune response in 3-D vaginal epithelial cells (ie, expression of CCL20, hBD-2, interleukin 1β, interleukin 6, interleukin 8, and tumor necrosis factor α) that can negatively affect barrier function. However, P. bivia and L. crispatus did not significantly upregulate pattern-recognition receptor-signaling, mucin expression, antimicrobial peptides/defensins, or proinflammatory cytokines in 3-D vaginal epithelial cell aggregates. Notably, L. iners induced pattern-recognition receptor-signaling activity, but no change was observed in mucin expression or secretion of interleukin 6 and interleukin 8.. We identified unique species-specific immune signatures from vaginal epithelial cells elicited by colonization with commensal and bacterial vaginosis-associated bacteria. A. vaginae elicited a signature that is consistent with significant disruption of immune barrier properties, potentially resulting in enhanced susceptibility to sexually transmitted infections during bacterial vaginosis.

Topics: Actinobacteria; Antimicrobial Cationic Peptides; Epithelial Cells; Epithelium; Female; Humans; Immunity, Innate; Interleukin-1beta; Interleukin-6; Interleukin-8; Lactobacillus; Microbiota; Mucins; Prevotella; Sexually Transmitted Diseases; Species Specificity; Vagina; Vaginosis, Bacterial

The purpose of this study was to assess the cervicovaginal levels of proinflammatory cytokines in women with Chlamydia trachomatis (CT) infection in the presence of bacterial vaginosis (BV) and normal flora and to compare with those negative for CT.. In this cross-sectional study, nonpregnant women were enrolled at 2 outpatient clinics and at 1 primary medical care unit in São Paulo State, Brazil. Cervicovaginal samples from 256 women with BV, of which 68 (26.6%) had concomitant CT infection and 188 (73.4%) were CT-negative, were measured for interleukin-1β (IL-1β), IL-6, and IL-8 by enzyme-linked immunosorbent assay. A matching number of samples from women with normal flora, CT-positive (n = 68) and negative (n = 188), were evaluated as control. Cytokine levels were compared by Mann-Whitney test and differences were considered significant at p < .05.. In CT-negative women, IL-1β was increased in BV (p < .001) when compared to normal flora, while the levels of IL-6 and IL8 were unchanged. The presence of CT infection was not associated with differences on cytokine levels in women with normal flora. However, women with BV had higher levels of IL-1β (p = .02), IL-6 (p = .02), and IL-8 (p = .03) in the presence of CT when compared to those who tested negative for CT.. Detection of endocervical CT is associated with increased cervicovaginal IL-1β, IL-6, and IL-8 levels in women with concomitant BV but not in those with normal flora.

Topics: Adolescent; Adult; Body Fluids; Brazil; Chlamydia Infections; Chlamydia trachomatis; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Lactobacillus; Middle Aged; Vagina; Vaginosis, Bacterial; Young Adult

hCAP18/LL-37 is the sole human cathelicidin; a family of host defence peptides with key roles in innate host defence. hCAP18/LL-37 is expressed primarily by neutrophils and epithelial cells, but its production and function in the lower genital tract is largely uncharacterised. Despite the significant roles for cathelicidin in multiple organs and inflammatory processes, its impact on infections that could compromise fertility and pregnancy is unknown. The aim of this study was to investigate cathelicidin production, regulation and function in the cervix. hCAP18/LL-37 was found to be present in cervicovaginal secretions collected from women in the first trimester of pregnancy and to be expressed at significantly higher levels in samples from women with alterations in vaginal bacterial flora characteristic of bacterial vaginosis. In endocervical epithelial cell lines, expression of the gene encoding hCAP18/LL-37 (CAMP) was not affected by TLR agonists, but was found to be up-regulated by both 1, 25 hydroxyvitamin D3 and 25 hydroxyvitamin D3. However, no association was found between serum levels of vitamin D and hCAP18/LL-37 concentrations in cervicovaginal secretions (n = 116). Exposure to synthetic LL-37 had a pro-inflammatory effect on endocervical epithelial cell lines, increasing secretion of inflammatory cytokine IL-8. Together these data demonstrate inducible expression of hCAP18/LL-37 in the female lower reproductive tract in vivo and suggest the capacity for this peptide to modulate host defence to infection in this system. Further investigation will elucidate the effects of hCAP18/LL-37 on the physiology and pathophysiology of labour, and may lead to strategies for the prevention of infection-associated preterm birth.

Topics: Adult; Antimicrobial Cationic Peptides; Calcifediol; Cathelicidins; Cell Line; Cervix Uteri; Cohort Studies; Cytokines; Epithelial Cells; Female; Humans; Interleukin-8; Pregnancy; Toll-Like Receptors; Vaginosis, Bacterial; Vitamin D

To evaluate levels of proinflammatory cytokines and sialidase activity in aerobic vaginitis (AV) in relation to normal vaginal flora and bacterial vaginosis (BV).. In this cross-sectional study, a total of 682 consecutive non-pregnant women attending the gynecology service were assessed and 408 women were included. Vaginal rinsing samples were collected from 223 women with microscopic finding of BV (n=98), aerobic vaginitis (n=25) and normal flora (n=100). Samples were tested for interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and sialidase activity.. Compared to women with normal flora, vaginal levels of IL-1β were highly increased in both BV and AV (p<0.0001). Significantly higher vaginal IL-6 was detected in AV (p<0.0001) but not in BV, in relation to normal flora. Women with AV also presented increased IL-8 levels (p<0.001), while those with BV presented levels similar to normal flora. Sialidase was increased in BV and AV compared with the normal group (p<0.0001) but no difference in sialidase activity was observed between BV and AV.. A more intense inflammatory host response occurs for AV than for BV when compared with normal flora. Furthermore, the increased sialidase activity in AV and BV indicates that both abnormal vaginal flora types can be harmful to the maintenance of a healthy vaginal environment.

Topics: Adolescent; Adult; Bacteria, Aerobic; Bacterial Proteins; Brazil; Cross-Sectional Studies; Female; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Middle Aged; Molecular Typing; Mucous Membrane; Neuraminidase; Up-Regulation; Vagina; Vaginal Smears; Vaginosis, Bacterial; Young Adult

To evaluate vaginal microflora and interleukin-1β (IL-β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) concentrations in the cervicovaginal fluid of a group of pregnant women in preterm labor when compared with a group of full-term pregnant women not yet in labor.. Case-control study performed in a University tertiary referral maternity in Campinas, Brazil with 45 pregnant women in preterm labor and 45 full-term pregnant women not in labor. All patients underwent speculum examination for the collection of cervicovaginal fluid. Bacterial vaginosis (BV) was diagnosed according to the criteria of Amsel and Nugent. Culture was performed for group B streptococcus (GBS) and lactobacilli, and hybrid capture assay for screening for chlamydial and gonococcal infection. Cytokine concentrations were measured using ELISA technique. Statistical analysis was performed using χ(2), Fisher's exact, and crude and adjusted odds ratios. Significance level was defined at 5%. The main outcome measures were cervicovaginal cytokines in preterm labor.. IL-6 and IL-8 were significantly associated with preterm labor. The changes in vaginal microflora, as well as BV and GBS, were more frequent in women in preterm labor, although BV and GBS showed no statistical significance. The presence of Candida sp., absence of lactobacilli, positive screening for chlamydial and gonococcal infection and the presence of IL-1β and TNF-α were not associated with preterm labor.. IL-6 and IL-8 and the presence of any type of vaginal infection were the factors that were significantly associated with preterm labor.

Topics: Adolescent; Adult; Body Fluids; Brazil; Case-Control Studies; Cytokines; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Tumor Necrosis Factor-alpha; Vagina; Vaginosis, Bacterial; Young Adult

Measurement of immune mediators and antimicrobial activity in female genital tract secretions may provide biomarkers predictive of risk for HIV-1 acquisition and surrogate markers of microbicide safety. However, optimal methods for sample collection do not exist. This study compared collection methods.. Secretions were collected from 48 women (24 with bacterial vaginosis [BV]) using vaginal and endocervical Dacron and flocked swabs. Cervicovaginal lavage (CVL) was collected with 10 mL of Normosol-R (n = 20), saline (n = 14), or water (n = 14). The concentration of gluconate in Normosol-R CVL was determined to estimate the dilution factor. Cytokine and antimicrobial mediators were measured by Luminex or ELISA and corrected for protein content. Endogenous anti-HIV-1 and anti-E. coli activity were measured by TZM-bl assay or E. coli growth.. Higher concentrations of protein were recovered by CVL, despite a 10-fold dilution of secretions, as compared to swab eluents. After protein correction, endocervical swabs recovered the highest mediator levels regardless of BV status. Endocervical and vaginal flocked swabs recovered significantly higher levels of anti-HIV-1 and anti-E. coli activity than Dacron swabs (P<0.001). BV had a significant effect on CVL mediator recovery. Normosol-R tended to recover higher levels of most mediators among women with BV, whereas saline or water tended to recover higher levels among women without BV. Saline recovered the highest levels of anti-HIV-1 activity regardless of BV status.. Endocervical swabs and CVL collected with saline provide the best recovery of most mediators and would be the optimal sampling method(s) for clinical trials.

Topics: Adult; alpha-Defensins; Analysis of Variance; Biomarkers; Cervix Uteri; Cytokines; Female; Genitalia, Female; HIV Infections; HIV-1; Humans; Interleukin-8; Mucous Membrane; Risk Factors; Secretory Leukocyte Peptidase Inhibitor; Solubility; Specimen Handling; Therapeutic Irrigation; Vagina; Vaginal Smears; Vaginosis, Bacterial; Young Adult

To examine cervicovaginal elafin production in pregnancy and determine its relationship in bacterial vaginosis.. Samples of cervicovaginal secretions were collected from women with uncomplicated singleton pregnancies (n = 112) below 20 weeks gestation. Bacterial flora was assessed using Nugent's criteria, and levels of elafin were measured by enzyme-linked immunosorbent serologic assay (ELISA). Elafin expression in the cervix was also examined by immunohistochemistry. In vitro expression of elafin was examined using cervix and vaginal cell lines.. Elafin is expressed in the cervical glandular epithelium. Elafin was found in all 112 samples of cervicovaginal secretions and levels were diminished in women with bacterial vaginosis (P < .05). Interleukin 1beta (IL-1beta) stimulated elafin expression in cells derived from the endocervix, but not in those derived from the vaginal epithelium.. Elafin is a component of cervicovaginal secretions in pregnancy, and levels are diminished in bacterial vaginosis. It may be an important component of innate immunity in the lower genital tract.

Topics: Adult; Cell Line; Cervix Uteri; Down-Regulation; Elafin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Interleukin-1beta; Interleukin-8; Mucous Membrane; Pregnancy; Pregnancy Trimester, First; RNA, Messenger; Vagina; Vaginosis, Bacterial

U. urealyticum, a member of the family Mycoplasmataceae, is often detected in the vagina of pregnant women. In this study, the possible association of ureaplasmal infection with preterm delivery was examined, as was the capacity of ureaplasmal LP to stimulate monocytes in vitro to produce pro-inflammatory cytokines relevant to preterm delivery. A hundred cases of normal delivery and 45 cases of preterm delivery were randomly selected. A mAb against U. urealyticum urease, that selectively and positively stained it in vaginal secretions of infected women but not in those of uninfected women, was generated. The preterm delivery group showed a significantly higher incidence of vaginal infection with this bacteria than the normal delivery group. Since the LP of Mycoplasma has potent biological activity, ureaplasmal LP was extracted. THP-1 cells, and human monocytic cells, produced IL-8, a potent pro-inflammatory cytokine associated with preterm delivery, and showed apoptotic cell death in response to the LP in vitro. These results suggest that U. urealyticum infection might play a causative role in preterm delivery via LP-induced IL-8 production and apoptosis.

Topics: Adult; Apoptosis; Cell Line; Female; Humans; Inflammation; Interleukin-8; Lipoproteins; Monocytes; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Prospective Studies; Random Allocation; Ureaplasma Infections; Ureaplasma urealyticum; Vagina; Vaginosis, Bacterial

Bacterial vaginosis (BV) has been associated with increased HIV cervicovaginal shedding. We hypothesized that this might relate to BV-associated increases in mucosal activated CD4 T cells, which could enhance local HIV replication.. Vaginal flora, cytokine/chemokine levels, and mucosal immune cell populations collected by cervical cytobrush were analyzed in 15 HIV-infected Kenyan female sex workers, before and after BV therapy with oral metronidazole.. Therapy reduced the Nugent score in all but 1 participant, and BV elimination was associated with reduced genital levels of interleukin 1beta(IL1beta), interleukin 8 (IL-8), and Regulated Upon Activation Normal T-cell Expressed and Secreted (RANTES). In addition, BV elimination reduced the total number of cervical CD4 T cells, including those expressing the HIV coreceptor CCR5 and the activation marker CD69.. BV induces significant and reversible alterations in cervical immune cell populations and local inflammatory cytokines that would be expected to enhance local HIV replication.

Topics: Anti-Bacterial Agents; CD4 Lymphocyte Count; Cervix Uteri; Chemokine CCL5; Female; HIV Infections; Humans; Interleukin-1beta; Interleukin-8; Metronidazole; Vaginosis, Bacterial; Virus Shedding

Bacterial vaginosis (BV) is associated with preterm labor, pelvic inflammatory disease (PID) and increased HIV acquisition, although the pathways that mediate these pathological effects have not been elucidated. To determine the presence of Toll-like receptor (TLR)-ligands and their specificity in BV, genital tract fluids were collected from women with and without BV by cervicovaginal lavage (CVL). The CVL samples were evaluated for their ability to stimulate secretion of proinflammatory cytokines and to activate NFkappaB and the HIV long terminal repeat (LTR), indicators of TLR activation, in human monocytic cells. Stimulation with BV CVLs induced higher levels of IL-8 and TNFalpha secretion, as well as higher levels of HIV LTR and NFkappaB activation, than CVLs from women with normal healthy bacterial flora. To identify which TLRs were important in BV, 293 cells expressing specific TLRs were exposed to CVL samples. BV CVLs induced higher IL-8 secretion by cells expressing TLR2 than CVLs from women without BV. Surprisingly, BV CVLs did not stimulate cells expressing TLR4/MD2, although these cells responded to purified lipopolysaccharide (LPS), a TLR4 ligand. BV CVLs, in cells expressing TLR2, also activated the HIV LTR. Thus, these studies show that soluble factor(s) present in the lower genital tract of women with BV activate cells via TLR2, identifying a pathway through which BV may mediate adverse effects.

Topics: Adult; Cell Line; Female; Genitalia, Female; HIV Long Terminal Repeat; Humans; Interleukin-8; NF-kappa B; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha; Vaginosis, Bacterial

To evaluate the local immune response in patients with bacterial vaginosis (BV) and cervical intraepithelial neoplasia (CIN), as assessed by cytokine and nitric oxide (NO) concentrations.. Patients attending for routine gynaecological examination were prospectively enrolled in groups: BV (n=25) diagnosed by clinical criteria, CIN graded I to III (n=35, 6 CIN I, 8 CIN II and 21 CIN III) by histological analysis, and controls (n=15) without clinical and cytological findings. Randomly selected patients within CIN group at grades II or III (n=15) were re-evaluated at 60 days after surgical treatment. Endocervical (EC) and vaginal secretion samples were collected by cytobrush and the levels of cytokines (ELISA) and NO metabolite (Griess reaction) were assayed.. NO was assessed in all subjects, and cytokines in all controls, 15 BV and 30 CIN patients. Interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and nitrite levels were higher in EC than in vaginal secretions in BV and CIN groups. In CIN group, IL-8, IL-10 and nitrite concentrations were greater in EC and/or vaginal secretions than in BV or controls. Surgical treatment reduced IL-8 levels in EC and vaginal secretions.. A similar local immune profile was found in BV and CIN groups. The increased local production of IL-8, IL-10 and NO in CIN suggests a role for these mediators in the immune response against tumour or tumour development.

Topics: Adolescent; Adult; Bodily Secretions; Cervix Uteri; Cytokines; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Middle Aged; Nitric Oxide; Prospective Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vagina; Vaginosis, Bacterial

Bacterial vaginosis is the most common vaginal disorder among women of reproductive age. The pathogenesis of bacterial vaginosis is poorly understood, but is defined by a transition in the vaginal flora from the predominant Lactobacillus species to other bacterial species such as Atopobium vaginae and Gardnerella vaginalis. This change is associated with an increase in vaginal cytokine secretion. We hypothesize that vaginal epithelial cells respond to bacterial vaginosis-associated bacteria by triggering an innate immune response. We observed that vaginal epithelial cells secreted interleukin-6 and interleukin-8 in response to Atopobium vaginae and Gardnerella vaginalis, but not to Lactobacillus crispatus. Atopobium vaginae induced increased levels of interleukin-6 and interleukin-8 transcripts, as well as increased transcripts for the antimicrobial peptide beta-defensin 4. This innate immune response required live bacteria capable of protein synthesis in direct contact with vaginal epithelial cells. The response of vaginal epithelial cells was mediated by Toll-like receptor 2, required the adaptor protein MyD88, and involved activation of the NFkappaB signaling pathway. These results suggest that Atopobium vaginae stimulates an innate immune response from vaginal epithelial cells, leading to localized cytokine and defensin production, and possibly contributes to the pathogenesis of bacterial vaginosis.

Topics: Actinobacteria; beta-Defensins; Cell Line; Epithelial Cells; Female; Gardnerella vaginalis; Gene Expression Profiling; Humans; Immunity, Innate; Interleukin-6; Interleukin-8; Lactobacillus; Myeloid Differentiation Factor 88; NF-kappa B; RNA, Messenger; Toll-Like Receptor 2; Vaginosis, Bacterial

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 aim of this study was to examine correlations between vaginal inflammatory cytokines (IL-1alpha, IL-1beta, IL-6 and IL-8) and pregnancy-related traits (gestational age, birth-weight, BMI, weight gain during pregnancy and vaginal pH). Differences in correlation coefficients were examined among bacterial vaginosis (BV) status and the presence or absence of mycoplasmas. A total of 105 women between the 22nd and 34th week of pregnancy were enrolled in this study. There was a strong negative correlation between IL-1alpha and weight gain during pregnancy (r=-0.877, p<0.001) and a strong positive correlation between IL-6 and BMI (r=0.670, p=0.024) in women with normal vaginal flora and mycoplasmas. These correlations were not present in women who had normal flora and no mycoplasmas. In women with BV and no mycoplasmas, there were significant correlations of gestational age with IL-6 (r=0.727, p=0.027) and IL-8 (r=0.689, p=0.040); however, these correlations were not significant in women with mycoplasmas. Our findings support the conclusion that correlations between inflammatory cytokines and pregnancy-related traits are dependent on context, suggesting that expression is labile. In particular, BMI and gestational age correlation differs depending on BV status and the presence or absence of BV-related mycoplasmas such as Mycoplasma hominis and Ureaplasma urealyticum.

Topics: Adult; Cohort Studies; Female; Humans; Interleukin-1alpha; Interleukin-1beta; Interleukin-6; Interleukin-8; Interleukins; Mycoplasma; Pregnancy; Pregnancy Complications, Infectious; Prospective Studies; Vagina; Vaginosis, Bacterial

The relative effect of HIV-1 infection compared with vaginal infections on vaginal cytokine concentrations is not well characterized. We compared vaginal fluid samples from HIV-1-infected women with those from HIV-negative women, to assess the effect of HIV-1 infection on concentrations of vaginal proinflammatory cytokines and the mucosal defense molecule secretory leukocyte protease inhibitor (SLPI). Twenty-seven HIV-1-infected women and 54 HIV-negative controls, matched for bacterial vaginosis (BV) status, had proinflammatory cytokine [interleukin (IL)-1beta, IL-6, IL-8] and SLPI concentrations measured from archived cervicovaginal lavage and vaginal swab samples using an enzyme-linked immunosorbent assay (ELISA). Log-transformed concentrations were compared by BV and HIV status in univariate analysis using Student's t-test, and in multivariate analysis using a linear regression model. In univariate analysis there were no significant differences in cytokine concentrations among HIV-1-infected and HIV-negative women. In a multivariable linear regression model, BV was significantly associated with an increase in IL-1 beta (p = 0.003). HIV infection was associated with an increased concentration of SLPI (p = 0.008), while BV status was significantly associated with a decrease in SLPI concentrations (p = 0.005). Neither HIV nor BV was associated with changes in IL-6 or IL-8. HIV does not have a major impact on vaginal concentrations of proinflammatory cytokines when controlling for the presence of bacterial vaginosis.

Topics: Adolescent; Adult; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; HIV Infections; HIV Seronegativity; HIV-1; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Middle Aged; Regression Analysis; Secretory Leukocyte Peptidase Inhibitor; Vagina; Vaginal Discharge; Vaginal Douching; Vaginosis, Bacterial

This study was undertaken to examine the influence of coinfections on vaginal innate and adaptive immunity, and microbial enzyme activities of pregnant women with bacterial vaginosis (BV).. The population consisted of 265 singleton pregnant women in early gestation (<20 weeks) with BV (Nugent 7-10) who had vaginal fluid collected for measurement of interleukin-1beta (IL-1beta) and IL-8 concentrations, number of neutrophils, immunoglobulin A against Gardnerella vaginalis (anti-Gvh IgA), and activities of microbial sialidase and prolidase.. Among women with BV, median levels of vaginal IL-1beta (4-fold, P = .005), IL-8 (4-fold, P < .001), and neutrophils (6-fold, P = .013) were greatly increased in women with T vaginalis with respect to women without any coinfection. Yeast increased the level of IL-8 (5-fold, P < .001), but not IL-1beta (P = .239) and neutrophils (P = .060). Chlamydia trachomatis and Neisseria gonorrhoeae had no effect on vaginal cytokines. None of the coinfections influenced vaginal anti-Gvh IgA, sialidase and prolidase activities.. The strong proinflammatory cytokine induction by T. vaginalis may contribute to the observed increase in preterm birth among BV positive women coinfected with T. vaginalis treated with metronidazole.

Topics: Adult; Animals; Chlamydia Infections; Chlamydia trachomatis; Dipeptidases; Female; Gonorrhea; Humans; Immunity; Immunity, Innate; Immunoglobulin A; Interleukin-1beta; Interleukin-8; Leukocyte Count; Mycoses; Neuraminidase; Neutrophils; Pregnancy; Pregnancy Complications, Infectious; Trichomonas Infections; Trichomonas vaginalis; Vagina; Vaginosis, Bacterial

Pregnancy has been considered to be a time of relative immune compromise. Lower-genital-tract immune response appears to be influenced by pregnancy. The objective of this study was to compare, in pregnant versus nonpregnant women, endocervical proinflammatory-cytokine expression in response to bacterial vaginosis.. Endocervical levels of interleukin (IL)-1 beta , IL-6, and IL-8 in 99 pregnant and 99 nonpregnant women, all with bacterial vaginosis and without concurrent sexually transmitted infections, were assessed by ELISA. Vaginal flora was characterized on the basis of quantitative vaginal cultures.. Women in the 2 groups differed with respect to smoking status and microbiological constituents responsible for bacterial vaginosis. When the data were stratified by these potential confounders, the levels of all 3 proinflammatory endocervical cytokines were significantly higher in pregnant women than in nonpregnant women.. The proinflammatory cytokine milieu in the cervix is enhanced in pregnant women with bacterial vaginosis, compared with that in nonpregnant women. The notion of pregnancy as an immune-compromised state may be anatomically compartment specific.

Topics: Adult; Cervix Uteri; Cytokines; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Pregnancy; Pregnancy Complications, Infectious; Vaginosis, Bacterial

The aim of this study was to estimate: the frequency of aerobic vaginitis, susceptibility of the GBS isolated from vagina of non-pregnant women with and without cervicitis to selected antibiotics and chemotherapeutics and the proinflammatory cytokines production by HeLa, THP-I, U - 937 cells after stimulation by vaginal GBS. Our results indicated low frequency of the aerobic vaginitis -4.5% among non-pregnant young women and ability of the vaginal GBS to release proinflammatory cytokines by human cell lines in vitro.

Topics: Adult; Anti-Bacterial Agents; Bacteria, Aerobic; Cells, Cultured; Coculture Techniques; Cytokines; Female; Gardnerella vaginalis; HeLa Cells; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Macrophage Activation; Male; Streptococcal Infections; Streptococcus agalactiae; Tumor Necrosis Factor-alpha; U937 Cells; Uterine Cervicitis; Vaginosis, Bacterial

To evaluate concentrations of interleukin (IL)-6, IL-8, lactoferrin (LF), and alpha defencine (alpha-DF) in the cervical mucus of pregnant women and analyze their relation to cervicitis and bacterial vaginosis (BV).. Cervical mucus samples were obtained from August 2003 through May 2004 from 157 women who were between the 6th and 36th week of an uncomplicated singleton pregnancy. All women were delivered at term, 69 without BV or cervicitis, 9 with BV, and 79 with cervicitis.. Interleukin 8, LF, and mu-DF concentrations were higher in women with cervicitis (0.81 +/- 0.36 pg/mL, 14.8+/-12.3 microg/mL, and 0.60 +/- 0.49 microg/mL) than in women without BV or cervicitis (0.35 +/- 0.34 pg/mL, 8.0 +/- 11.0 microg/mL, and 0.15 +/- 0.12 microg/mL). Interleukin 6 concentration was higher in women with BV (0.26 +/- 0.32 pg/mL) than in women without BV or cervicitis (0.09 +/- 0.15 pg/mL) or in women with cervicitis (0.12 +/- 0.18 pg/mL).. Higher levels of inflammatory cytokines in the cervical mucus of pregnant women may lead to early detection of lower genital tract infection.

Topics: Adult; alpha-Defensins; Biomarkers; Cervix Mucus; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Gestational Age; Humans; Interleukin-6; Interleukin-8; Lactoferrin; Pancreatic Elastase; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Infectious; Regression Analysis; Uterine Cervicitis; Vaginosis, Bacterial

This study was undertaken to assess if levels of interleukin-1beta (IL-1beta), IL-8, sialidase, prolidase and immunoglobulin A against Gardenerella vaginalis hemolysin (anti-Gvh IgA) in vaginal secretions differ between BV+ women with (M+) and without (M-) Mobiluncus spp.. Vaginal secretions were obtained from 265 women at their first prenatal care visit and assessed for all study parameters. Gram stain evaluation using Nugent criteria was performed and coinfection with sexually transmitted infections determined. Differences between BV+/M+ and BV+/M- women were evaluated using the chi2 statistic or Mann-Whitney test.. Of the 265 BV+ women, 43% (n = 113) were M+ of which 97% (n = 110) had Nugent scores of 9 or 10 . BV+/M+ women had elevated levels of sialidase (median value: 4.11 nmol vs 1.91 nmol of converted substrate; P = .003) but no difference in prolidase, anti-Gvh IgA, IL-1beta, IL-8, levels were found between the two groups. BV+/M- women had significantly higher rates of coinfection with Trichomonas vaginalis.. BV+/M+ women have higher vaginal concentrations of sialidase and lower rates of T. vaginalis compared with BV+/M- women. Further research is needed to assess the association of this, and other, microbiologic profiles to risk of adverse pregnancy outcome.

Topics: Actinomycetales Infections; Adult; Dipeptidases; Female; Gardnerella vaginalis; Humans; Immunoglobulin A; Interleukin-1; Interleukin-8; Mobiluncus; Neuraminidase; Pregnancy; Pregnancy Complications, Infectious; Trichomonas Vaginitis; Vagina; Vaginal Smears; Vaginosis, Bacterial

The aim of this study was to investigate the relationship between the concentration of selected proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6 and IL-8) in cervicovaginal fluid, as measured in midgestation, and the risk of early-onset neonatal infection (EONI).. Cervicovaginal fluids were obtained from a cohort of 114 pregnant women at 22 to 34 weeks' gestation. The samples were analyzed for the concentrations of selected proinflammatory cytokines using standard enzyme-linked immunosorbent assay technique (ELISA). Lower genital tract microbiology was diagnosed using Gram stain method according to Spiegel's criteria and by culture.. Mean gestational age at the time of sampling was 29.0 weeks. Mean time between sampling and delivery was 9.3 (SD 4.7) weeks. Bacterial vaginosis (BV) was diagnosed in 27.2% of subjects and M. hominis and U. urealyticum in 22.8% and 26.3%, respectively. Out of 114 women examined, 20 (17.5%) delivered newborns with EONI. Median cervicovaginal concentrations of IL-1alpha, IL-1beta, IL-6 and IL-8 did not differ between women who delivered newborns with EONI as compared to women who delivered newborns without EONI. Women with pathological lower genital tract microflora and low IL-8 concentration (below 25(th) percentile) during pregnancy presented a significant risk of delivering newborns with EONI (OR=4.9; 95% CI, 1.1-22.8). Subjects with pathological lower genital tract microflora and a low concentration of more than one cytokine had the highest risk of delivering a newborn with EONI, OR=16.2, 95% CI, 1.1-234.0.. Cytokine measurement in cervicovaginal fluid in early gestation could be useful for predicting subsequent EONI only among pregnant women with lower genital tract infection. Maternal genital tract immune hyporesponsiveness as represented by low concentrations of proinflammatory cytokines may create a permissive environment for ascending infection and may lead to subsequent EONI.

Topics: Cervix Mucus; Cervix Uteri; Female; Humans; Infant, Newborn; Infections; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Interleukins; Mycoplasma hominis; Pregnancy; Pregnancy Complications, Infectious; Risk Factors; Ureaplasma urealyticum; Vagina; Vaginosis, Bacterial

Bacterial vaginosis is a common condition associated with increased risk of sexually transmitted diseases, including human immunodeficiency virus infections. In contrast, vulvovaginal candidiasis has a much weaker association with sexually transmitted diseases. We found that vaginal lavage fluid from women with bacterial vaginosis is deficient in antimicrobial polypeptides and antimicrobial activity compared to fluid from healthy women or women with vulvovaginal candidiasis. Effective treatment normalized the concentrations of antimicrobial polypeptides in both bacterial vaginosis and in vulvovaginal candidiasis, suggesting that the abnormalities were a result of the diseases. Unlike in vulvovaginal candidiasis, the neutrophil attractant chemokine interleukin-8 (IL-8) was not increased in bacterial vaginosis, accounting for low concentrations of neutrophil-derived defensins in vaginal fluid. In organotypic cultures of human vaginal epithelium containing dendritic cells, treatment with Lactobacillus jensenii, a typical vaginal resident, induced the synthesis of IL-8 mRNA and the epithelial human beta-defensin-2 mRNA, but a typical bacterial vaginosis pathogen, Gardnerella vaginalis, had no effect. When the two bacteria were combined, Gardnerella vaginalis did not interfere with the immunostimulatory effect of Lactobacillus jensenii. The loss of normal immunostimulatory flora in bacterial vaginosis is thus associated with a local deficiency of multiple innate immune factors, and this deficiency could predispose individuals to sexually transmitted diseases.

Topics: Adult; Antimicrobial Cationic Peptides; beta-Defensins; Body Fluids; Cytokines; Female; Gardnerella vaginalis; Humans; Hydrogen-Ion Concentration; Interleukin-8; Lactic Acid; Lactobacillus; RNA, Messenger; Vaginal Douching; Vaginosis, Bacterial

Interleukin-8 (IL-8) may play a role in the activation of the vaginal immune system during bacterial vaginosis. However, contradictory results were obtained regarding the involvement of IL-8 in the immunological response during bacteria vaginosis. These apparently contradictory results could be due to different genetic variations of the study groups. Since some gene polymorphisms may affect the level of IL-8 production, the aim of this study was to determine whether the frequency IL-8 promoter alleles and levels of IL-8 in vaginal fluid are associated with bacterial vaginosis during pregnancy. Genotyping for IL-8 polymorphisms in the promoter region of the gene was performed in 34 pregnant women with asymptomatic bacterial vaginosis matched for gestational age with 38 pregnant women without vaginosis. Additionally, vaginal IL-8 levels were assayed by the dual monoclonal antibody sandwich enzyme-linked immunosorbent assay technique. The frequencies of the three polymorphisms were not significantly different between control women and women with bacterial vaginosis. In addition, there was no linkage disequilibrium between the polymorphisms. Furthermore, there was no statistical difference in median vaginal levels of IL-8 between both groups. Neither the frequencies of IL-8 polymorphic alleles nor levels of IL-8 in vaginal fluid were associated with bacterial vaginosis.

Topics: Adult; Female; Gene Frequency; Humans; Interleukin-8; Polymorphism, Genetic; Pregnancy; Pregnancy Complications, Infectious; Promoter Regions, Genetic; Vagina; Vaginosis, Bacterial

During pregnancy cytokines and inflammatory mediators stimulate the expression of prostaglandin, the levels of which determine the onset of labor. The aim of this work was to study interleukin IL-1beta, IL-6 and IL-8 levels in the vaginal discharge, serum and urine of pregnant women with genitourinary infection before and after specific treatment. One hundred and fifty-one patients were studied during the second or third trimester of their pregnancy.. The selected patients were: healthy or control group (n = 52), those with bacterial vaginosis (n = 47), those with vaginitis (n = 37), those with asymptomatic urinary infection (n = 15) and post-treatment. The level of cytokines was assayed by ELISA test. The Mann-Whitney U-test was used for statistical analysis.. The IL-1beta levels in vaginal discharge were: control 103.5 +/- 24.2 pg/ml, bacterial vaginosis 1030 +/- 59.5, vaginitis 749.14 +/- 66.7l ( p < 0.0001), post-treatment 101.4 +/- 28.7. IL-6 values were similar in both control and infected groups, and there were no patients with chorioamnionitis. In vaginal discharge IL-6: control 14.2 +/- 3.9 pg/ml, bacterial vaginosis 13.2 +/- 3.8, vaginitis 13 +/- 4.2. IL-8 levels were: control 1643 +/- 130.3 pg/ml, bacterial vaginosis 2612.7 +/- 257.7, vaginitis 3437 +/- 460 (p < 0.0001), post-treatment 1693 +/- 126.6. In urine the results were: control 40.2 +/- 17 pg/ml, asymptomatic urinary infection 1200.7 +/- 375 (p < 0.0001). In patients with therapeutic success both IL-1beta and IL-8 returned to normal levels.. Genitourinary infections induce a significant increase in IL-1beta and IL-8 levels in vaginal secretions, and IL-8 in urine as well. Both cytokines could be useful as evolutive markers of infection.

Topics: Body Fluids; Cytokines; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Obstetric Labor Complications; Pregnancy; Pregnancy Complications, Infectious; Vaginosis, Bacterial

Recent studies have suggested that proinflammatory cytokines might play a crucial role in the mechanism of preterm labour and delivery. The main aim of this prospective study was to evaluate the usefulness of selected proinflammatory cytokines' (IL-1 alpha, IL-1 beta, IL-6 and IL-8) levels in cervico-vaginal fluid of pregnant women as an early marker of preterm delivery.. Cervico-vaginal fluids were obtained from 107 pregnant women at 22 to 34 weeks' gestation, including 61 women with threatened preterm labour (TPL) and 46 women with physiological course of pregnancy (reference group). Those samples were analyzed for the concentrations of selected cytokines using standard enzyme-linked immunosorbent assay technique (ELISA). Lower genital tract microbiology was diagnosed using Gram stain method according to Spiegel's criteria and by culture.. Mean gestational age at the time of sampling was 28.6 weeks. Mean time between sampling and delivery was 8,24 weeks in TPL group and 10.2 weeks in reference group. BV was diagnosed in 25.2% of subjects under study. M. hominis and U. urealyticum were diagnosed more frequently among women from TPL group (25.9% vs 14.9% and 36.2% vs 17.0%, respectively). Out of 107 women 15 (14.0%) delivered before 37th week of gestation. The rate of preterem delivery was significantly higher in threatened preterm labour group--21.3% is comparison to reference group--4.3%. Median cervico-vaginal concentration of IL-1 alpha, IL-1 beta, IL-6 and IL-8 did not differ between preterm and term delivery group. Only women with lower genital tract infection and one cytokine's low concentration (below 25th percentile) presented a higher risk of preterm delivery--OR=2,91. If IL-1 alpha and IL-1 beta concentrations were below 25th percentile, the calculated risk of preterm delivery was OR = 4.65. The highest risk was noted for women with lower genital tract infection and low cervico-vaginal concentrations of IL-1 alpha and IL-8--OR = 8.0 (3.20-20.01).. The early gestation cytokines' levels in cervico-vaginal fluid of pregnant women could be useful for prediction of preterm delivery only among women with lower genital tract infection.

Topics: Biomarkers; Cervix Mucus; Comorbidity; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant, Newborn; Interleukin-1; Interleukin-6; Interleukin-8; Obstetric Labor, Premature; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Infectious; Prospective Studies; Risk Assessment; Vagina; Vaginal Smears; Vaginosis, Bacterial

Vaginal innate immunity in response to microbial perturbation is still poorly understood and could be crucial for protection from adverse outcomes. We investigated the relationship between interleukin (IL)-8, IL-1beta and neutrophils in vaginal fluid obtained from 60 healthy women and 51 women who were bacterial vaginosis (BV) positive. Concentrations of IL-8 and IL-1beta were highly correlated with counts of neutrophils in vaginal fluid of the entire population examined (111 subjects). Vaginal IL-1beta concentrations were significantly higher (P < 0.001) in BV positive women. There was no significant difference in IL-8 levels or number of neutrophils between healthy controls and BV positive women. None of the healthy controls with high neutrophil counts (> or =75th percentile, 14 average count per field) had high concentrations of IL-1beta (> or =75th percentile, 220 pg/ml), whereas 84% of BV positive women with high neutrophil counts had high IL-1beta concentrations (P < 0.001). On the contrary, no difference in the percentage of subjects with elevated concentrations of IL-8 (> or =75th percentile, 2842 pg/ml) was found between healthy and BV positive women with high numbers of neutrophils (55.5% of healthy versus 53% of BV positive women). Our findings show that BV causes a large increase in IL-1beta concentrations which is not paralleled by an increase in IL-8 concentrations in vaginal fluid, suggesting that BV-associated factors more specifically dampen IL-8 rather than IL-1beta. The lack of an increase in IL-8 may explain the absence of an increase in neutrophil numbers in most women exposed to abnormal vaginal colonization (BV).

Topics: Female; Humans; Interleukin-1; Interleukin-8; Leukocyte Count; Neutrophils; Reference Values; Vagina; Vaginosis, Bacterial

Topics: Biomarkers; Cytokines; Female; Humans; Inflammation; Interleukin-1; Interleukin-8; Pilot Projects; Pregnancy; Pregnancy Complications, Infectious; Vaginosis, Bacterial

Recent studies have suggested that proinflammatory cytokines might play a crucial role in the mechanism of preterm labour and delivery. Lower genital tract infection could also influence the cytokines levels. The main aim of this study was to compare the concentrations of interleukin (IL)-1 alpha, IL-1 beta, IL-6 and IL-8 in cervicovaginal fluid of pregnant women with threatened preterm labour (TPL) with group of women with normal course of pregnancy (reference group) and to determine impact of lower genital tract microflora on cytokines concentration.. Cervicovaginal fluids were obtained by lavage from 40 pregnant women at 22 to 34 weeks' gestation. Those samples were analyzed for the concentrations of selected cytokines using standard enzyme-linked immunosorbent assay technique. Lower genital tract microbiology was diagnosed using Gram stain method according to Spiegel's criteria. TPL was defined as uterine contractions treated by tocolysis.. Threatened preterm labour (TPL) was diagnosed in 22 (55.0%) cases. Mean gestational age at the time of cytokines measurement was 28.6 weeks. Mean concentrations of IL-1 alpha, IL-1 beta and IL-8 measured in cervicovaginal fluid of pregnant women with TPL and in reference group were similar (89.43 vs. 91.17 pg/ml; 42.05 vs. 41.01 pg/ml and 621.8 vs. 697.8 pg/ml, respectively). Vaginal levels of IL-6 was higher among women with preterm labour (21.1 pg/ml vs. 13.9 pg/ml) as compared to reference group. Bacterial vaginosis (BV) was diagnosed in 11 women (27.5%) while grade I microflora in 19 (47.5%). There was a positive correlation between BV and IL-1 alpha and IL-1 beta concentration but no with IL-6 and IL-8.. Vaginal levels of IL-6 were found to be significantly elevated among women with threatened preterm labour while IL-1 alpha and IL-1 beta among women with BV. The usefulness of cytokines measurement in cervicovaginal fluid of pregnant women for prediction of preterm delivery should be clarified in further after excluding the impact of lower genital tract infections on cytokines concentrations.

Topics: Adult; Biomarkers; Case-Control Studies; Cervix Mucus; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Risk Factors; Time Factors; Tocolytic Agents; Vagina; Vaginal Smears; Vaginosis, Bacterial

Mucosal immune system activation may represent a critical determinant of adverse consequences associated with bacterial vaginosis (BV), such as sexual human immunodeficiency virus transmission, upper genital tract infections, postsurgical infections, and adverse pregnancy outcomes. Concentrations of sialidase, prolidase, and anti-Gardnerella vaginalis hemolysin (Gvh) immunoglobulin A (IgA) were higher in vaginal fluids of 75 fertile women with BV, compared with concentrations in vaginal fluids of 85 healthy control subjects. Interleukin (IL)-8 levels were positively associated with anti-Gvh IgA response and inversely correlated with high levels of prolidase and sialidase in women with BV. IL-8 concentration was strongly associated with leukocyte count in both healthy and BV-positive women. The absence of leukocytes in most women with BV likely is due to lack of IL-8 induction. Parallel impairment of innate and adaptive mucosal immune factors, likely through microbial hydrolytic effects, may allow for the ascent of microorganisms to the upper genital tract and may facilitate viral infections.

Topics: Adult; Bacterial Infections; Dipeptidases; Female; Gardnerella vaginalis; Hemolysin Proteins; Humans; Immunoglobulin A; Interleukin-8; Leukocyte Count; Middle Aged; Neuraminidase; Vagina; Vaginosis, Bacterial

To determine whether vaginal interleukin-6, interleukin-8, neutrophils, bacterial vaginosis, and selected vaginal bacteria are predictors of amniotic fluid (AF) infection among women in preterm labor.. One hundred ninety-seven afebrile women in preterm labor with intact membranes had vaginal and AF samples collected for Gram stain, culture, and interleukin-8 and interleukin-6 determinations. Vaginal interleukin-6, interleukin-8, neutrophils, and vaginal flora were compared in women with positive and negative AF cultures. The negative AF culture group was subdivided according to AF interleukin-6 concentration. Logistic regression was used to examine the associations between vaginal cytokines and flora and AF infection or elevated AF interleukin-6.. The vaginal interleukin-8 concentration and neutrophil count were significantly higher with both AF infection and elevated concentrations of AF interleukin-6 and interleukin-8. The vaginal interleukin-6 concentration was not associated with AF infection or high concentration of AF cytokines. Amniotic fluid infection was associated with bacterial vaginosis or intermediate vaginal flora by Gram stain, absence of hydrogen peroxide-producing Lactobacillus, and presence of vaginal Bacteroides ureolyticus and Fusobacterium. Vaginal interleukin-8 levels greater than 30 ng/mL had 80% sensitivity and a positive predictive value of 35%, and an abnormal vaginal Gram stain (more than five neutrophils per 400x field, bacterial vaginosis species, or intermediate flora) had 90% sensitivity and a positive predictive value of 27% to detect AF infection or elevated AF interleukin-6.. A high vaginal interleukin-8 concentration, abnormal vaginal Gram stain, absent hydrogen peroxide-producing Lactobacillus, and anaerobic vaginal flora were strongly associated with AF infection among women in preterm labor.

Topics: Adult; Bacteriological Techniques; Chorioamnionitis; Female; Humans; Interleukin-6; Interleukin-8; Leukocyte Count; Neutrophils; Obstetric Labor, Premature; Pregnancy; Vagina; Vaginosis, Bacterial

To investigate the prevalence of bacterial vaginosis (BV) and abnormal bacterial vaginal flora in an infertile population and correlate with cervical cytokine production and in vitro fertilization (IVF) outcome.. In a blinded study, 331 asymptomatic IVF patients were evaluated for BV, abnormal vaginal flora and cervical cytokine production (interleukin 1 beta [IL-1 beta] and IL-8) on the day of oocyte retrieval. All patients received tetracycline prophylaxis at the time of oocyte retrieval.. BV was identified in 4.2% (14/331) of the patients. Patients with idiopathic infertility were more likely to have BV than were women with other causes of infertility (P = .02 vs. male factor, P = .03 vs. tubal factor and P < .01 vs. endometriosis-associated infertility). Patients with abnormal vaginal flora had higher cervical IL-1 beta and IL-8 cytokine levels as compared to patients with normal vaginal flora. IL-1 beta and IL-8 levels in the study subjects correlated highly. No differences were detected in IVF outcome parameters based on the vaginal flora determined at the time of retrieval.. Abnormal vaginal flora, including that causing BV, is associated with elevated cervical levels of IL-1 beta and IL-8. The induction of proinflammatory cytokines by an altered vaginal ecosystem may be a previously unrecognized cause of idiopathic infertility.

Topics: Adult; Cervix Uteri; Cytokines; Embryo Transfer; Enzyme-Linked Immunosorbent Assay; Female; Fertilization in Vitro; Gardnerella vaginalis; Humans; Infertility, Female; Interleukin-1; Interleukin-8; Mycoplasma hominis; New York; Pregnancy; Pregnancy Rate; Prevalence; Vagina; Vaginosis, Bacterial

The purpose was to determine the prognostic value of interleukin (IL) 1-alpha, IL-6 and IL-8 in cervico/vaginal secretion for preterm birth (<37 weeks of gestation) in twin pregnancies.. The study included screening of 121 women with twin pregnancies with sampling at 24, 26, 28, 30, 32 and 34 weeks of gestation. IL-1alpha, IL-6 and IL-8 was analyzed with ELISA immunoassays. The detection limit was 30 pg/mL for IL-1 and IL-8 and 40 pg/mL for IL-6. Vaginal fluid was smeared and dried for later evaluation of bacterial vaginosis (presence of clue cells).. Spontaneous preterm birth occurred in 36 women and 65 women were delivered at term. IL-8 was significantly higher (p=0.03) in samples from women delivered preterm (median 3.72 ng/g mucus, range <0.07-220.00) compared with samples from women delivered at term (median 3.03 ng/g mucus, range <0.08-378.60). At 28 weeks of gestation, IL-8 (cut off 1.75 ng/g mucus) was associated with preterm delivery (relative risk 2.2, CI 95% 1.1-4.5) with a sensitivity, specificity, positive and negative predictive value of 78.8, 45.8, 44.8 and 79.4%, respectively. The levels of IL-1alpha and IL-6 were not significantly associated with preterm birth. Bacterial vaginosis was found in 47/541 (8.7%) samples analyzed. The levels of IL-1alpha and IL-8 were significantly higher in samples positive for bacterial vaginosis than in negative samples (p<0.0001 and p<0.01, respectively). There was no significant association between the level of IL-6 and bacterial vaginosis.. IL-8, but not IL-1alpha and IL-6, was associated with preterm delivery but the relationship was too weak to be of predictive value for preterm birth in twin pregnancies. IL-1alpha and IL-8, but not IL-6, were associated with bacterial vaginosis.

Topics: Adult; Cervix Uteri; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-1; Interleukin-6; Interleukin-8; Middle Aged; Obstetric Labor, Premature; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; ROC Curve; Sensitivity and Specificity; Vagina; Vaginosis, Bacterial