interleukin-8 and Genital-Diseases--Female

Efficacy and safety of panipenem/betamipron (PAPM/BP) in treatment of obstetric and gynecological infections, and change of interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in blood, as markers of infection, were investigated. The results were as follows; 1) Clinical efficacy of PAPM/BP by drip infusion of 1-2 g/day for 3-14 days against 52 patients with intrauterine infection (n = 29), pelveoperitonitis (n = 19), and other infections were 14 "Excellent" in 14 cases, "Good" in 35 cases, and efficacy rate was 94.2% (49/52). Both efficacy rate analy by causative organisms and eradication rate were 35/37 (94.6%). No subjective or objective side effects and no abnormal labolatory findings were observed. 2) Changes of IL-6 (> 4 pg/ml) levels in serum, as an infection marker, were observed in 8 cases out of 14 cases (57.1%), and correlation between CRP and IL-6 in the treatment process was noticed. However, changes of serum IL-8 (> 12.5 pg/ml) were observed in only 2 cases of those 14 cases (14.3%), indicative that IL-8 has no significance as a marker of infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; beta-Alanine; Biomarkers; Drug Therapy, Combination; Female; Genital Diseases, Female; Humans; Interleukin-6; Interleukin-8; Middle Aged; Pelvic Inflammatory Disease; Peritonitis; Thienamycins; Uterine Diseases

Women in Africa, especially young women, have very high human immunodeficiency virus (HIV) incidence rates that cannot be fully explained by behavioral risks. We investigated whether genital inflammation influenced HIV acquisition in this group.. Twelve selected cytokines, including 9 inflammatory cytokines and chemokines (interleukin [IL]-1α, IL-1β, IL-6, tumor necrosis factor-α, IL-8, interferon-γ inducible protein-10 [IP-10], monocyte chemoattractant protein-1, macrophage inflammatory protein [MIP]-1α, MIP-1β), hematopoietic IL-7, and granulocyte macrophage colony-stimulating factor, and regulatory IL-10 were measured prior to HIV infection in cervicovaginal lavages from 58 HIV seroconverters and 58 matched uninfected controls and in plasma from a subset of 107 of these women from the Centre for the AIDS Programme of Research in South Africa 004 tenofovir gel trial.. HIV seroconversion was associated with raised genital inflammatory cytokines (including chemokines MIP-1α, MIP-1β, and IP-10). The risk of HIV acquisition was significantly higher in women with evidence of genital inflammation, defined by at least 5 of 9 inflammatory cytokines being raised (odds ratio, 3.2; 95% confidence interval, 1.3-7.9; P = .014). Genital cytokine concentrations were persistently raised (for about 1 year before infection), with no readily identifiable cause despite extensive investigation of several potential factors, including sexually transmitted infections and systemic cytokines.. Elevated genital concentrations of HIV target cell-recruiting chemokines and a genital inflammatory profile contributes to the high risk of HIV acquisition in these African women.

Topics: Africa; Cervix Uteri; Chemokine CCL2; Chemokines; Cytokines; Disease Susceptibility; Female; Genital Diseases, Female; Genitalia, Female; HIV Infections; Humans; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-6; Interleukin-8; Sexually Transmitted Diseases; South Africa; Tumor Necrosis Factor-alpha; Uterine Cervicitis; Vagina; Vaginal Douching; Vaginitis; Young Adult

In mammals, Toll-like receptors (TLRs) are the principal family of innate immune pattern recognition receptors (PRRs). The main function for TLRs is the detection of molecular patterns associated with invading pathogens. We investigated TLR expression and function in three established human endometrial epithelial cell lines, including hTERT-EEC, HEC-1B and Ishikawa cells, and clarified the application of these endometrial cell lines as in vitro models for studying TLR expression and function in the female reproductive tract. TLR gene expression was examined by RT-PCR and protein localization by immunohistochemistry. Our results showed that TLR expression in these cell lines is comparable to published literature on TLR expression in primary human endometrial tissue. TLR function was investigated by the detection of IL-6 and IL-8 production by ELISA in response to TLR2, TLR3, TLR5, TLR7 and TLR9 ligands. We found that hTERT-EEC cells were responsive to TLR5 ligand and HEC-1B cells respond to TLR3 and TLR5 ligands. In contrast, Ishikawa cells respond only to PMA/I which was used as a positive control for IL-8 production. Finally, we investigated the influence of flagellin as a TLR5 stimulant on TLR5 expression in these cell lines by QPCR. Our results showed that the endometrial cell lines showed a tendency for increased TLR5 expression in response to flagellin stimulation and in hTERT-EEC cells this tendency was statistically significant. These results suggest that hTERT-EEC, HEC-1B and Ishikawa cell lines can be used as in vitro models to investigate innate immune responses of endometrial cells in the female reproductive tract.

Topics: Cell Line; Endometrium; Epithelial Cells; Female; Flagellin; Genital Diseases, Female; Humans; Immunity, Innate; Interleukin-6; Interleukin-8; Toll-Like Receptors

TNF-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor (TNF) cytokine superfamily which regulates a number of cellular responses, including inflammation and proliferation. TWEAK is primarily secreted by phagocytic cells and its receptor, fibroblast growth factor-inducible 14 (Fn14), is expressed on non-lymphoid cells, including epithelial, endothelial and mesenchymal cells. The TWEAK/Fn14 pathway is highly conserved from an evolutionary standpoint, and has been shown to play a role in tissue regeneration and inflammation in the liver, kidney, lung and skeletal muscle. We hypothesized that TWEAK/Fn14 might have a physiological role in regulating infection-induced inflammation in the lower female genital tract. To test this hypothesis, we examined expression of the receptor Fn14 in relevant cells and tissue. Receptor function was tested by treating cells with recombinant TWEAK, with and without other known proinflammatory stimuli. Flow cytometric analysis of vaginal and cervical epithelial cells revealed that Fn14 was highly expressed at the cell surface. We also detected both Fn14 and TWEAK in whole cervical tissue by RT-PCR. Treatment of vaginal and cervical epithelial cells with recombinant TWEAK led to a weak induction of the chemokine IL-8. However, TWEAK potentiated the effects of IL-1ss, the TLR2 ligand Pam(3)CysSK(4), and live Neisseria gonorrhoeae in a synergistic manner. These data reveal a novel pathway for regulation of microbial-induced inflammation in the female reproductive tract and suggest that interference with the TWEAK/Fn14 pathway might be an approach to abrogate excessive infection-induced inflammation caused by sexually transmitted pathogens.

Topics: Animals; Cell Line; Cervix Uteri; Cytokine TWEAK; Female; Genital Diseases, Female; Gonorrhea; Humans; Inflammation; Interleukin-1beta; Interleukin-8; Lipopeptides; Mice; Neisseria gonorrhoeae; Receptors, Tumor Necrosis Factor; Toll-Like Receptor 2; Tumor Necrosis Factors; TWEAK Receptor; Vagina

High levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have been demonstrated in the peritoneal fluid of benign and malignant gynaecological disease. Peritoneal monocytes and macrophages, endometrial cells, endometrial and peritoneal stromal cells and tumour cells produce these cytokines in vitro. To investigate whether normal human peritoneal mesothelial cells (HPMC) produce IL-6 and IL-8, HPMC were isolated from omental biopsies. Primary HPMC (P-HPMC) were transfected with pSV3-neo encoding SV40 large T antigen (T-HPMC) to generate sufficient cells. T-HPMC preserved the characteristics of P-HPMC as assessed by phase contrast microscopy, electron microscopy, immunocytochemistry and flow cytometry (FACS) analysis. T-HPMC retained a stable phenotype up to passage 14-19, whereas P-HPMC proliferated poorly and became senescent by passage 4-6. T-HPMC and P-HPMC constitutively expressed IL-6 and IL-8 at both protein and mRNA level. IL-6 and IL-8 production was stimulated by recombinant human interleukin-1beta (hIL-1beta) or human tumour necrosis factor-alpha (hTNF-alpha) alone in a dose-dependent manner. Moreover, hIL-1beta or hTNF-alpha up-regulated IL-6 and IL-8 gene expression as determined by competitive PCR. In contrast, human interferon-gamma (hIFN-gamma) or lipopolysaccharide (LPS) showed no effect. These data indicate that (1) T-HPMC lines mimic the morphological and functional features of P-HPMC, (2) P-HPMC and T-HPMC constituitively produce IL-6 and IL-8, which is enhanced by hIL-1beta and hTNF-alpha and (3) HPMC in vivo may participate in the pathogenesis of benign and malignant gynaecological disease.

Topics: Antigens, Polyomavirus Transforming; Ascitic Fluid; Cells, Cultured; Epithelial Cells; Female; Genes, Viral; Genital Diseases, Female; Humans; Interferon-gamma; Interleukin-1; Interleukin-6; Interleukin-8; Lipopolysaccharides; Phenotype; Recombinant Proteins; RNA, Messenger; Simian virus 40; Transfection; Tumor Necrosis Factor-alpha; Up-Regulation

Topics: Female; Genital Diseases, Female; Genital Neoplasms, Female; Humans; Interleukin-8; Reference Values