interleukin-8 and Uterine-Cervical-Dysplasia

Interleukins-6 and -8 are two pro-inflammatory cytokines increasing in serum and local levels under malignant conditions. There are limited evidences on the association between cervical level of these two factors and cervical intraepithelial neoplasia (CIN). So, this study aimed to explore the association between cervical levels of IL-6 and IL-8 with cervical premalignant lesions.. The present case-control study was conducted on married women undergone Pap smear for routine screening in two groups as the group with CIN (n=100) and the healthy control group (n=100). Cervical secretions were collected using sterile swab and the levels of IL-8 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). The obtained data were analyzed by SPSS software.. The mean cervical IL-6 level was 568.66±594.62 pg/ml in the patients with CIN and 212.7±213.9 pg/ml in the controls (P <0.001). The cervical IL-8 levels in the case and control groups were measured to be 1320.43±876.5 pg/ml and 1053.59±747.64 pg/ml, respectively (p=0.02). By modifying the confounding size effect of the age and marital duration, it was determined that cervical levels of IL-6 and IL-8 were both associated with CIN.. Our results showed that the cervical levels of IL-6 and IL-8 are associated with CIN independent of age and marital dura.

Topics: Adult; Age Factors; Case-Control Studies; Female; Humans; Interleukin-6; Interleukin-8; Iran; Marriage; Middle Aged; Papanicolaou Test; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Young Adult

inflammatory cytokines have been associated with various cancers, including cervical cancers. Interpreting cytokine expression in liquid based cervical samples is quite challenging. This study is aimed at evaluating the levels of interleukin 8 and 10 in liquid based cervical samples.. this is a descriptive analytical study carried out on eighty five (85) subjects aged between 23 and 68 years. Cervical samples were collected in liquid based medium and smears later examined after staining with Papanicolaou technique. These were categorized into low grade intra-epithelial lesion/malignancy, high grade intraepithelial lesion/malignancy according to the degree of dyskaryosis. Concentrations of interleukin 8 and interleukin 10 in the samples were determined by enzyme linked immunosorbent assay.. the mean age, standard deviation (SD) of the study subjects were 40.6 (7.8) years. A total number of 79 females (92.9%) were negative for intra-epithelial lesion/malignancy (NILM), while 4 (4.71%) and 2 (2.35%) were positive for low grade intra-epithelial lesion/malignancy (LILM) and high grade intra-epithelial lesion (HILM) respectively. While mean levels of interleukin 8 increased with the degree of malignancy, (107.27 ± 11.88pg/ml) in LILM, (114.80 ± 2.12pg/ml) in HILM when compared with NILM (88.39 ± 18.06pg/ml), (f = 0.700, p = 0.018); the mean levels of interleukin 10 was comparable between these groups (p ≥ 0.05). Pearson correlation coefficient analysis showed a negative association between interleukin 8 and interleukin 10 (r = -1.999, p = 0.000) in LILM.. interleukin 8 cytokines in cervical cancer is associated with the degree of malignancy. Possible anti-inflammatory effect of interleukin 10 was not observed.

Topics: Adult; Aged; Cervix Uteri; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-8; Middle Aged; Papanicolaou Test; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears; Young Adult

Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-β1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil. We analysed 108 healthy uninfected women (HC) and 108 HPV-positive women with cervical lesions. Genetic polymorphisms were assessed using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism. Comparison of the distribution of the genotypic and allelic frequencies of the IL-18 +396 T>G polymorphism between HPV infected woman an uninfected controls showed that the GG genotype and G allele were both more frequent in the HC group, and were associated with protection from HPV infection (p = 0.0015; OR = 0.29 CI95% = 0.13-0.61; p = 0.0005; OR = 0.45 CI95% 0.29-0.7, respectively). Individuals from the control group could have previously had HPV infection that was spontaneously eliminated; however, it was undetectable at the time of sample collection. Based on our findings, we hypothesize that the IL-8 +396 G>T polymorphism could interfere with susceptibility to HPV infection, by modulating the ability of immune system to fight the virus.

Topics: Adolescent; Adult; Aged; Alleles; Base Sequence; Brazil; Cross-Sectional Studies; DNA, Viral; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Interleukin-6; Interleukin-8; Middle Aged; Papillomavirus Infections; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Transforming Growth Factor beta1; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Young Adult

Immune responses in the uterine cervix are considered to play an important role in persistent human papillomavirus (HPV) infection and carcinogenesis, but many aspects of the mechanism are still unclear. The goal of this study was to measure cytokines to analyze immune responses in patients with cervical intraepithelial neoplasia (CIN).. The levels of 17 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, INF-γ, MCP-1, MIP-1β, and TNFα) in cervical mucus were simultaneously measured using a multiplex immunoassay in 52 high-grade squamous intraepithelial lesion (HSIL) cases and overproduction of IL-1β, IL-8, and MIP-1β was identified. The levels of these 3 cytokines were measured in 130 patients with or without CIN lesions using enzyme-linked immunosorbent assay. The associations of the cytokine levels with the cytology, infecting HPV type, and status of cigarette smoking were investigated.. IL-1β and IL-8 levels were associated with the cytology, and these levels were higher in HSIL cases than in NILM (negative for intraepithelial lesion and malignancy) and LSIL (low-grade squamous intraepithelial lesion) cases (P = 0.005, P = 0.001, respectively). The MIP-1β level was significantly lower in smokers (P = 0.018) and high-risk (HR)-HPV-infected patients (P = 0.021).. Enhanced expression of IL-1β and IL-8 indicates that Th2 inflammatory responses become stronger in the local uterine cervical region with the progression of CIN lesions, and a decrease in the MIP-1β level may be advantageous for immunoescape of HPV. Cigarette smoking may further facilitate persistent HPV infection.

Topics: Adult; Asian People; Chemokine CCL4; Disease Progression; Female; Humans; Interleukin-1beta; Interleukin-8; Mucous Membrane; Papillomavirus Infections; Smoking; Squamous Intraepithelial Lesions of the Cervix; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Chemokines play a role in tumor-inflammation and angiogenesis that could be involved in tumor progression. Monocyte chemoattractant protein-1 (MCP-1), Interleukin-8 (IL-8) and macrophage inflammatory proteins (MIP) have been identified in tumor tissues of patients with different neoplasms. Therefore, the aim of the current study was to investigate the expressions of MCP-1, IL-8 and MIP-1α, mononuclear leukocyte infiltration and leukocyte/chemokine expressions in cervical tissues from patients with cervical intraepithelial neoplasia (CIN) and controls. MCP-1, IL-8 and MIP-1α expressions and leukocyte infiltration were determined by indirect immunofluorescence in cervix biopsies from CIN patients (n=65) and 7 normal controls. Increased expressions of MCP-1 and IL-8 in CIN were observed. Increment of lymphocyte infiltration and coexpression of CD3/MCP-1 and CD3/IL-8 were found in CIN. CD3/MCP-1 cell percentage was found decreased and CD3/IL-8 percentage increased according to the CIN evolution. MIP-1α remained similar to control values. The increased expression of MCP-1 and IL-8 in cervical neoplasia may lead to tumor progression.

Topics: Chemokine CCL2; Chemokine CCL3; Chemokines; Female; Humans; Interleukin-8; Leukocytes; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection.. The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57).. Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time.. HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV.

Topics: Adolescent; Adult; Aged; Blotting, Southern; Cross-Sectional Studies; Cytokines; Escherichia coli; Female; Humans; Inflammation; Interleukin-1alpha; Interleukin-1beta; Interleukin-8; Middle Aged; New York; Papillomavirus Infections; Prevalence; Reproductive Tract Infections; Risk Factors; Therapeutic Irrigation; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Young Adult

We observed diminished lymphoproliferation to multiple stimuli in older women with persistent cervical human papillomavirus (HPV) infection. Adipokines are a class of inflammatory cytokines that are altered in some persistent infections. The objective was to compare the level of adipokines and inflammatory cytokines in heparinized plasma from women with persistent HPV cervical infection (Cases, N=50, oversampled for their weak lymphoproliferation responses) with women with no evidence of persistent HPV cervical infection (Controls, N=50, oversampled for their strong lymphoproliferation responses). Plasma samples were analyzed with multiplex assays for adipokines and inflammatory cytokines. Cases had significantly elevated plasma levels of resistin (p<0.0001) and sFas (p=0.0038) as compared to controls. Risk of persistent HPV infection increased significantly with increasing levels of resistin and 8Fas. This is the first study to demonstrate elevated levels of resistin and sFas in HPV persistently infected, older women with decreased immune function expanding the understanding of the systemic inflammation and immune alterations in individuals persistently infected with HPV. Further studies within a larger cohort are needed to define the generalities of these findings and any role adipokines have in persistent HPV infection.

Topics: Adipokines; Alphapapillomavirus; fas Receptor; Female; Genotype; Humans; Inflammation Mediators; Interleukin-8; Middle Aged; Papillomavirus Infections; Resistin; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

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

Immunological status, levels of pro-inflammatory cytokines of non-specific resistance and tumor expression factor have been studied in patients with cervical dysplasia or cancer versus stage. Slight and moderate dysplasia involved virtually no changes in interleukin-8 (Il-8) and tumor necrotic factor TNF-alpha concentrations whereas those of Il-1 alpha and Il-1 beta were 5 times as high. Monocyte-dependent expression of tissue factor was similar to that in healthy women. In cases of advanced dysplasia and cervical carcinoma, monocyte-dependent expression of tissue factor and production of Il-1 alpha, Il-1 beta, Il-8 and TNF-alpha were significantly enhanced. Patients with cervical carcinoma stage II and III revealed signs of depression of the cellular component of immunity as well as non-specific resistance. Hence, increased concentrations of cytokines induce monocyte-dependent expression of tissue factor in advanced dysplasia and cervical carcinoma by triggering-on of hypercoaggulation.

Topics: Adult; Cytokines; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-1; Interleukin-8; Middle Aged; Neoplasm Staging; Thrombophilia; Thromboplastin; Tumor Necrosis Factor-alpha; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms