interleukin-8 and Chlamydia-Infections

Chlamydia/Chlamydophila are a family of intracellular gram-negative bacteria that infect their hosts primarily via mucosal epithelia. Chronic disease associated with bacterial persistence, inflammation and tissue damage are common sequelae of infection with these organisms. Human epithelial cell lines respond to infection by releasing pro-inflammatory cytokines and chemokines such as interleukin (IL)-6 and IL-8, and upregulating the expression of mRNA encoding Ikappa-Balpha, the endogenous inhibitor of NF-kappaB. However, Ikappa-Balpha is not upregulated in response to bacterial lipopolysaccharide (LPS). The failure of epithelial cells to respond to LPS is associated with the absence of surface expression of CD14. Identification of the components of Chlamydia/Chlamydophila that can induce pro-inflammatory mediators coupled with the mechanisms by which epithelial cells detect infection and respond accordingly will advance the development of preventative strategies.

Topics: Chlamydia; Chlamydia Infections; Chlamydophila; Chlamydophila Infections; Gene Expression Regulation, Bacterial; HeLa Cells; Humans; I-kappa B Proteins; Interleukin-6; Interleukin-8; NF-KappaB Inhibitor alpha

An investigation was carried out to determine the therapeutic effect of levofloxacin (LVFX) once-a-day oral therapy at the dose of 200 mg/day for 7 days on uterine cervicitis, in comparison with LVFX twice-a-day oral therapy at the dose of 200 mg/day for 7 days. Of the 102 patients enrolled in the study, 90 were subjected to the analysis. The efficacy rate on uterine cervicitis of the once-a-day therapy and twice-a-day therapy groups according to the evaluation of the Drug Efficacy Evaluation Committee were 72.0% (36/50) and 82.5% (33/40), respectively. The efficacy rate on uterine chlamydial cervicitis of the once-a-day therapy and twice-a-day therapy groups according to the evaluation of the Drug Efficacy Evaluation Committee were 88.0% (22/25) and 85.7% (18/21), respectively. Safety was evaluated as "safe" in 88 of the 90 assessable patients (97.8%). Side effects were seen in two cases, which belong to the once-a-day therapy group; mild candidiasis and mild breast distension sense. As the antimicrobial treatment started, the levels of the inflammatory cytokines, interleukin-6 (IL-6) and interleukin-8 (IL-8) in the cervical mucus, decreased. It is suggested that IL-6 and IL-8 can be useful indicators of the antimicrobial treatment in the uterine cervicitis. These results suggested that the LVFX once-a-day therapy can be useful on uterine cervicitis.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Chlamydia Infections; Drug Administration Schedule; Female; Humans; Interleukin-6; Interleukin-8; Levofloxacin; Middle Aged; Mucus; Ofloxacin; Uterine Cervicitis

Chlamydia suis intestinal infection of single-animal experimental groups of gnotobiotic newborn piglets was previously reported to cause severe, temporary small intestinal epithelium damage. We investigated archived intestinal samples for pro-inflammatory nuclear factor kappa B (NF-κB) activation, Interleukin (IL)-6 and IL-8 production and immune cell influx. Samples were collected 2, 4 and 7 days post-inoculation with C. suis strain S45/6 or mock inoculum (control). Increased nuclear localization of epithelial NF-κB, representative of activation, in the jejunum and ileum of C. suis-infected animals, compared to uninfected controls, began by 2 days post-infection (dpi) and persisted through 7 dpi. Infected animals showed increased production of IL-8, peaking at 2 dpi, compared to controls. Infection-mediated CD45-positive immune cell influx into the jejunal lamina propria peaked at 7 dpi, when epithelial damage was largely resolved. Activation of NF-κB appears to be a key early event in the innate response of the unprimed porcine immune system challenged with C. suis. This results in an acute phase, coinciding with the most severe clinical symptoms, diarrhea and weight loss. Immune cells recruited shortly after infection remain present in the lamina propria during the recovery phase, which is characterized by reduced chlamydial shedding and restored intestinal epithelium integrity.

Topics: Animals; Chlamydia; Chlamydia Infections; Diarrhea; Feces; Germ-Free Life; Host-Pathogen Interactions; Immunity, Cellular; Immunohistochemistry; Interleukin-6; Interleukin-8; Intestinal Mucosa; Models, Animal; NF-kappa B; Swine; Swine Diseases

Atherosclerosis is a progressive disease characterized by chronic inflammation of the arterial walls, associated with genetic and infectious factors. The present study investigated the involvement of

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Atherosclerosis; Brazil; C-Reactive Protein; Chlamydia Infections; Chlamydia trachomatis; Chlamydophila pneumoniae; Female; Genetic Association Studies; Genetic Predisposition to Disease; Heart Valve Diseases; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Polymorphism, Genetic; Prevalence; Promoter Regions, Genetic; Risk; Tumor Necrosis Factor-alpha; Young Adult

Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection worldwide and known to increase the risk for HIV acquisition. Few studies have investigated how infection of epithelial cells compromises barrier integrity and antimicrobial response.. ECC-1 cells, a human uterine epithelial cell line, were treated with live and heat-killed C. trachomatis. Epithelial barrier integrity measured as transepithelial resistance (TER), chemokines antimicrobial levels, and antimicrobial mRNA expression was measured by ELISA and Real-time RT-PCR.. Epithelial barrier integrity was compromised when cells were infected with live, but not with heat-killed, C. trachomatis. IL-8 secretion by ECC-1 cells increased in response to live and heat-killed C. trachomatis, while MCP-1, HBD2 and trappin2/elafin secretion decreased with live C. trachomatis.. Live C. trachomatis suppresses ECC-1 innate immune responses by compromising the barrier integrity, inhibiting secretion of MCP-1, HBD2, and trappin-2/elafin. Differential responses between live and heat-killed Chlamydia indicate which immune responses are dependent on ECC-1 infection rather than the extracellular presence of Chlamydia.

Topics: Anti-Infective Agents; beta-Defensins; Cell Line; Chemokine CCL2; Chlamydia Infections; Chlamydia trachomatis; Elafin; Epithelial Cells; Female; Gene Expression Regulation; Hot Temperature; Humans; Immunity, Innate; Immunomodulation; Interleukin-8; Tumor Necrosis Factor-alpha; Uterus

To investigate latent conjunctival Chlamydia trachomatis (CT) and Bacteroides fragilis (BF) infections as potential risk factors for posttrabeculectomy bleb failure.. This retrospective observational study included 50 primary open-angle glaucoma eyes of 50 patients who were submitted to trabeculectomy without cytostatics from September 2010 to June 2011 and were followed up for at least a year. Preoperatively, conjunctival scrapings were taken and their specimens subjected to polymerase chain reaction, direct fluorescent assay and cell culture testing for CT, and culture for BF on blood agar medium. Serum CT-specific IgG and IgA and tear interleukin (IL)-1β and IL-8 concentrations were measured with enzyme-linked immunosorbent assay. We defined bleb failure as intraocular pressure >21 mm Hg with antiglaucoma medications, resulting from reduced bleb filtration capacity due to bleb fibrosis, fistula obstruction, flattened bleb, or encapsulated bleb, and no earlier than 2 weeks after surgery. At the time of the reintervention, a scleroconjunctival biopsy was obtained for histopathology (including direct fluorescent assay testing for CT). Eyes were divided into a failure group and a nonfailure group, depending on whether they developed bleb failure (required reintervention) or not within a follow-up year.. In the failure group (n=18), the frequencies of detection of CT and BF in conjunctival specimens were 27.8% and 66.7%, respectively, versus 0% and 9.4% in the nonfailure group (n=32). CT and BF were detected in 11.1% and 11.1%, respectively, of scleroconjunctival biopsies. IgG and IgA seropositivity to CT was found in 66.7% and 33.3%, respectively, of the failure group patients, versus 9.4% and 0% of the nonfailure group patients. Tear IL-1β and IL-8 levels were markedly elevated in the failure group (468.83±80.43 and 107.89±15.11 pg/mL, respectively) versus the nonfailure group (22.34±5.43 and 9.34±2.83 pg/mL, respectively).. Being a contributor to low-grade conjunctival inflammation, latent conjunctival CT, and BF infections in primary open-angle glaucoma patients represent risk factors for posttrabeculectomy bleb failure.

Topics: Aged; Antibodies, Bacterial; Bacteroides fragilis; Bacteroides Infections; Chlamydia Infections; Chlamydia trachomatis; Conjunctivitis, Bacterial; Eye Infections, Bacterial; Eye Proteins; Female; Fluorescent Antibody Technique, Direct; Glaucoma, Open-Angle; Humans; Immunoglobulin A; Immunoglobulin G; Interleukin-1beta; Interleukin-8; Intraocular Pressure; Male; Middle Aged; Polymerase Chain Reaction; Postoperative Complications; Retrospective Studies; Risk Factors; Tears; Tonometry, Ocular; Trabeculectomy; Treatment Failure

Previous studies have given conflicting results about the effect of generally infection and Chlamydia trachomatis on seminal ILs and semen parameters. The aim of this study was to investigate the relationship between semen quality and the level of seminal interleukins (ILs) in infertile couples with C. trachomatis. Blood, first void urine (FVU) and semen were obtained from 250 infertile men who had failed to conceive after 12 months of trying. Serological analysis for specific IgA, IgM and IgG antibodies to C. trachomatis in serum, the presence of C. trachomatis in FVU and semen sample and semen analysis were carried out. The main results are as follows: (i) elevated IL-6 and IL-8 are observed in C. trachomatis-positive men, but this is not significant and it varies by diagnostic method; and (ii) IL-6 and IL-8 levels were correlated with each other and the concentration of leucocytes, but IL-8 was correlated with semen volume and patient's age. This study showed that men with such an infection in FVU samples (PCR positive) had only lower semen volume compared with men without infection.

Topics: Adult; Antibodies, Bacterial; Biomarkers; Chlamydia Infections; Chlamydia trachomatis; Humans; Infertility, Male; Inflammation; Interleukin-6; Interleukin-8; Iran; Male; Middle Aged; Polymerase Chain Reaction; Semen; Semen Analysis; Young Adult

Chlamydia trachomatis is the most common cause of curable bacterial sexually transmitted infections worldwide. Although the pathogen is well established, the pathogenic mechanisms remain unclear. Given the current challenges of antibiotic resistance and blocked processes of vaccine development, the use of a specific chlamydiaphage may be a new treatment solution. φCPG1 is a lytic phage specific for Chlamydia caviae, and shows over 90% nucleotide sequence identity with other chlamydiaphages. Vp1 is the major capsid protein of φCPG1. Purified Vp1 was previously confirmed to inhibit Chlamydia trachomatis growth. We here report the first attempt at exploring the relationship between Vp1-treated C. trachomatis and the protein and gene levels of the mitogen-activated/extracellular regulated protein kinase (MAPK/ERK) pathway by Western blotting and real-time PCR, respectively. Moreover, we evaluated the levels of pro-inflammatory cytokines interleukin (IL)-8 and IL-1 by enzyme-linked immunosorbent assay after Vp1 treatment. After 48 h of incubation, the p-ERK level of the Vp1-treated group decreased compared with that of the Chlamydia infection group. Accordingly, ERK1 and ERK2 mRNA expression levels of the Vp1-treated group also decreased compared with the Chlamydia infection group. IL-8 and IL-1 levels were also decreased after Vp1 treatment compared with the untreated group. Our results demonstrate that the inhibition effect of the chlamydiaphage φCPG1 capsid protein Vp1 on C. trachomatis is associated with the MAPK pathway, and inhibits production of the pro-inflammatory cytokines IL-8 and IL-1. The bacteriophages may provide insight into a new signaling transduction mechanism to influence their hosts, in addition to bacteriolysis.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Capsid Proteins; Cell Line; Chlamydia Infections; Chlamydia trachomatis; Humans; Interleukin-1; Interleukin-8; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Phosphorylation; RNA Phages; Signal Transduction

Chlamydia is one of the most common sexually transmitted diseases in humans worldwide, causing chronic lesions in the reproductive tract. Due to its often asymptomatic course, there is limited knowledge about the initial changes in the genital tract following infection. This study employs a novel sexually mature minipig model to investigate the initial histopathological changes following vaginal infection with Chlamydia trachomatis serovar D.. A vaginal inoculation resulted in an infection primarily affecting the lower genital tract. The histopathological changes were characterized by a subepithelial inflammation consisting of neutrophils and mononuclear cells, followed by an increase in the number of plasma cells within the sub-epithelial stroma of the vagina. Detection of Chlamydia was associated with expression of cyclooxygenase-2 and interleukin-8 by superficial epithelial cells. The infection was self-limiting, with a duration of 7 days.. Neutrophils, plasma cells and IL-8 have been linked with Chlamydia genital infection of unknown duration in human patients. In this study, we observe a similar pattern of local immune response/inflammation following experimental inoculation suggesting this porcine model shows promise as a model for translational chlamydia research.

Topics: Animals; Chlamydia Infections; Chlamydia trachomatis; Cyclooxygenase 2; Epithelial Cells; Female; Interleukin-8; Serogroup; Swine; Swine Diseases; Swine, Miniature; Vagina

Chlamydia trachomatis and Chlamydia pneumoniae are important human pathogens that infect the urogenital/anorectal and respiratory tracts, respectively. Whilst the ability of these bacteria to infect epithelia is well defined, there is also considerable evidence of infection of leucocytes, including dendritic cells (DCs). Using a human dendritic cell line (MUTZ), we demonstrate that the infection and replication of chlamydiae inside DCs is species and serovar specific and that live infection with C. pneumoniae is required to upregulate costimulatory markers CD80, CD83 and human leucocyte antigen (HLA)-DR on MUTZ cells, as well as induce secretion of interleukin (IL)-2, IL-6, IL-8, IL-12 (p70), interferon-gamma and tumour necrosis factor-alpha Conversely, C. trachomatis serovar D failed to upregulate DC costimulatory markers, but did induce secretion of high concentrations of IL-8. Interestingly, we also observed that infection of MUTZ cells with C. pneumoniae or C. trachomatis serovar L2, whilst not replicative, remained infectious and upregulated lymph node migratory marker CCR7 mRNA. Taken together, these data confirm the findings of other groups using primary DCs and demonstrate the utility of MUTZ cells for further studies of chlamydial infection.

Topics: Antigens, CD; B7-1 Antigen; CD83 Antigen; Cell Line; Chlamydia Infections; Chlamydia trachomatis; Chlamydophila Infections; Chlamydophila pneumoniae; Dendritic Cells; Epithelial Cells; HLA-DR Antigens; Humans; Immunoglobulins; Interferon-gamma; Interleukin-12; Interleukin-2; Interleukin-6; Interleukin-8; Membrane Glycoproteins; Receptors, CCR7; Tumor Necrosis Factor-alpha

An important question in the study of chlamydial genital tract disease is why some women develop severe upper tract disease while others have mild or even "silent" infections with or without pathology. Animal studies suggest that the pathological outcome of an infection is dependent upon both the composition of the infecting chlamydial population and the genotype of the host, along with host physiological effects, such as the cyclical production of reproductive hormones and even the size of the infecting inoculum or the number of repeated infections. In this study, we compared two variants of Chlamydia caviae, contrasting in virulence, with respect to their abilities to ascend the guinea pig genital tract. We then determined the effect of combining the two variants on the course of infection and on the bacterial loads of the two variants in the genital tract. Although the variants individually had similar infection kinetics in the cervix, SP6, the virulent variant, could be isolated from the oviducts more often and in greater numbers than the attenuated variant, AZ2. SP6 also elicited higher levels of interleukin 8 (IL-8) in the lower genital tract and increased leukocyte infiltration in the cervix and uterus compared to AZ2. When the two variants were combined in a mixed infection, SP6 outcompeted AZ2 in the lower genital tract; however, AZ2 was able to ascend the genital tract as readily as SP6. These data suggest that the ability of SP6 to elicit an inflammatory response in the lower genital tract facilitates the spread of both variants to the oviducts.

Topics: Animals; Chlamydia; Chlamydia Infections; Disease Models, Animal; Female; Guinea Pigs; Humans; Interleukin-8; Reproductive Tract Infections

Chlamydia abortus is an obligate intracellular bacterium that is an important cause of ovine abortion worldwide. There are reports of abortions in cattle, but these are very rare compared to the reported incidence in sheep. The bacterium is transmitted oro-nasally and can establish a sub-clinical infection until pregnancy, when it can invade the placenta and induce an inflammatory cascade leading to placentitis and abortion. Early host-pathogen interactions could explain differential pathogenesis and subsequent disease outcome in ruminant species. In this study, we assessed the ability of sheep and cattle oro-nasal turbinate cells to sense and respond to C. abortus infection. The cells expressed toll like receptor (TLR) 2, TLR4, nucleotide oligomerization domain (NOD) 1 and NOD-like receptor pyrin domain containing 3 (NLRP3) mRNA. In response to C. abortus infection, both ovine and bovine turbinate cells produce CXCL8 mRNA and protein late in the bacterial developmental cycle, but do not produce IL-1β or TNF-α. The UV-inactivated bacteria did not elicit a CXCL8 response, suggesting that intracellular multiplication of the bacteria is important for activating the signalling pathways. The production of innate immune cytokines from cattle and sheep turbinate cells in response to C. abortus infection was found to be largely similar.

Topics: Abortion, Veterinary; Animals; Cattle; Cattle Diseases; Cells, Cultured; Chlamydia Infections; Cytokines; Female; Host-Pathogen Interactions; Immunity, Innate; Interleukin-8; Pregnancy; Receptors, Pattern Recognition; RNA, Messenger; Sheep; Sheep Diseases; Sheep, Domestic; Species Specificity; Turbinates

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

The endocervical epithelium is a major reservoir for Chlamydia trachomatis in women, and genital infections are extended in their duration. Epithelial cells act as mucosal sentinels by secreting cytokines and chemokines in response to pathogen challenge and infection. We therefore determined the signature cytokine and chemokine response of primary-like endocervix-derived epithelial cells in response to a common genital serovar (D) of C. trachomatis. For these studies, we used a recently-established polarized, immortalized, endocervical epithelial cell model (polA2EN) that maintains, in vitro, the architectural and functional characteristics of endocervical epithelial cells in vivo including the production of pro-inflammatory cytokines. PolA2EN cells were susceptible to C. trachomatis infection, and chlamydiae in these cells underwent a normal developmental cycle as determined by a one-step growth curve. IL1α protein levels were increased in both apical and basolateral secretions of C. trachomatis infected polA2EN cells, but this response did not occur until 72h after infection. Furthermore, protein levels of the pro-inflammatory cytokines and chemokines IL6, TNFα and CXCL8 were not significantly different between C. trachomatis infected polA2EN cells and mock infected cells at any time during the chlamydial developmental cycle up to 120h post-infection. Intriguingly, C. trachomatis infection resulted in a significant decrease in the constitutive secretion of T cell chemokines IP10 and RANTES, and this required a productive C. trachomatis infection. Examination of anti-inflammatory cytokines revealed a high constitutive apical secretion of IL1ra from polA2EN cells that was not significantly modulated by C. trachomatis infection. IL-11 was induced by C. trachomatis, although only from the basolateral membrane. These results suggest that C. trachomatis can use evasion strategies to circumvent a robust pro-inflammatory cytokine and chemokine response. These evasion strategies, together with the inherent immune repertoire of endocervical epithelial cells, may aid chlamydiae in establishing, and possibly sustaining, an intracellular niche in microenvironments of the endocervix in vivo.

Topics: Cell Line; Cervix Uteri; Chemokine CCL5; Chemokines; Chlamydia Infections; Chlamydia trachomatis; Cytokines; Epithelial Cells; Female; Humans; Inflammation; Interleukin-11; Interleukin-1alpha; Interleukin-6; Interleukin-8; Receptors, Cytokine; Receptors, Interleukin-1; Tumor Necrosis Factor-alpha

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen and the etiologic agent of blinding trachoma. Intracellular signaling pathways leading to host cell inflammation and innate immunity to Chlamydia include those mediated by Toll-like receptors (TLRs) and nucleotide binding oligomerization domain 1 (Nod1) protein. In epithelial cells, TLR-dependent signaling contributes to local immune responses via induction of inflammatory mediators. There is evidence that TLR3, TLR4, and, particularly, TLR2 are critical for Chlamydia-mediated host cell activation and pathology. Despite the importance of TLR2, major chlamydial TLR2 antigens have not been identified so far. Numerous bacterial porins are known TLR2 agonists, i.e., porins from Neisseriae, Shigella, Salmonella, Haemophilus influenzae, and Fusobacterium nucleatum, which share structural and functional similarities with the chlamydial major outer membrane protein (MOMP), a strong antigen candidate for a potential vaccine against C. trachomatis. We describe the ability of purified, detergent-free MOMP to signal via TLR2 in vitro in TLR-overexpressing cells and TLR2-competent human reproductive tract epithelial cell lines. Using MOMP formed in pure protein micelles (proteosomes), we show the induction of TLR2-dependent interleukin-8 (IL-8) and IL-6 secretion in vitro, the involvement of TLR1 as a TLR2 coreceptor, and the activation of both NF-κB and mitogen-activated protein (MAP) kinase intracellular pathways. Interestingly, MOMP proteosomes induce cytokine secretion in endocervical epithelial cells (End/E6E7) but not in urethral epithelial cells (THUECs). A detailed understanding of the TLR2-dependent molecular mechanisms that characterize the effect of MOMP proteosomes on host cells may provide new insights for its successful development as an immunotherapeutic target against Chlamydia.

Topics: Bacterial Outer Membrane Proteins; Cell Line; Cell Line, Tumor; Chlamydia Infections; Chlamydia trachomatis; Epithelial Cells; HEK293 Cells; HeLa Cells; Humans; Interleukin-6; Interleukin-8; Micelles; Mitogen-Activated Protein Kinases; NF-kappa B; Porins; Proteasome Endopeptidase Complex; Signal Transduction; Toll-Like Receptor 1; Toll-Like Receptor 2

Chlamydia pneumoniae heat shock protein (cHSP) 60 is produced during chronic chlamydial infection and activate innate immune and inflammatory responses thereby contributing to atherogenesis. However, to date there is no apparent signaling cascade delineated in human atherosclerotic plaques in C. pneumoniae positive coronary artery disease (CAD) patients. Atherosclerotic plaques were obtained from 40 CAD patients (28 men, 12 women) attending Department of Cardio Thoracic and Vascular Surgery Safdarjung Hospital, New Delhi. Atherosclerotic plaques were used for gene expression studies at RNA level by real-time PCR and to study expression of ERK1/2, JNK1/2, NF-kB, IkkB and MCP-1 at protein level by immunoblotting. Significantly higher (p < 0.001) RNA expression was found for IL-8, TLR-2/4, TGF-β, ICAM1, VCAM1 and MAPKinase genes, whereas significantly lower (p < 0.001) RNA expression for SMAD4, IkkB, BRCA1 and IL-10 was detected in cHSP60-positive atheromatous plaque of CAD patients. Moreover, at proteins level pERK1/2 (p = 0.05), NF-kB (p = 0.017), MCP-1 (p = 0.011) was higher and IkkB expression was lower (p = 0.038) in cHSP60-positive atheromatous plaque of CAD patients. This study by using human atheromatous plaques at RNA and protein levels demonstrated higher expression of TLR-2/4, IL-8, ICAM1, VCAM1, ERK1/2 and NF-kB in cHSP60-positive CAD patients.

Topics: Adult; Chaperonin 60; Chemokine CCL2; Chlamydia Infections; Coronary Artery Disease; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Interleukin-8; Male; MAP Kinase Kinase 4; Middle Aged; NF-kappa B; Plaque, Atherosclerotic; Signal Transduction; Toll-Like Receptor 4

In this study, the role of Chlamydia pneumoniae in triggering platelets to induce the inflammatory potential chemokines CCL3, CCL5, CCL7 and CXCL8 in atherosclerotic patients was investigated.. Venous blood from control subjects (n = 35) and atherosclerotic patients (n = 35) was collected in tubes with and without EDTA. Platelets from controls and patients were separated from whole blood and then stimulated with lipopolysaccharide (LPS), live C. pneumoniae and heat-treated C. pneumoniae. The ability of C. pneumoniae and its LPS to stimulate platelets and expression of CCL3, CCL5, CCL7 and CXCL8 was assessed with immunofluorescence. Immunosorbent assays were used to detect anti-C. pneumoniae antibodies in sera from patients and healthy subjects.. Nonstimulated platelets from patients showed significant expression of CCL3, CCL5, CCL7 and CXCL8 compared to controls (p < 0.0001). Stimulation of platelets from patients with live and heat-treated C. pneumoniae and its LPS demonstrated significant induction of chemokines compared to similarly stimulated platelets from controls (p < 0.01). After stimulation with heat-treated C. pneumoniae chemokine expression in platelets from controls was significantly lower than after stimulation with live C. pneumoniae (p < 0.01), which was not the case when platelets from patients were stimulated. Increased levels of anti-C. pneumoniae antibodies were detected in sera from patients compared to healthy subjects, suggesting prior C. pneumoniae exposure.. Our data demonstrated an interactive link between C. pneumoniae and platelets in atherosclerotic patients, leading to induction of potential chemokines and possibly disease development.

Topics: Adult; Arteriosclerosis; Blood Platelets; Case-Control Studies; Chemokine CCL3; Chemokine CCL5; Chemokine CCL7; Chemokines; Chlamydia Infections; Chlamydophila pneumoniae; Female; Humans; Immunoenzyme Techniques; Interleukin-8; Male; Middle Aged; Thrombosis

Different cellular and biochemical markers have been proposed as indicators of infection-inflammation of male genital tract.. Semen samples from 80 men attending an andrologic clinic were evaluated to determine the presence of leukocyte, bacteria, antibodies against Chlamydia trachomatis, levels of IL-6, IL-8, IL-10, and TNF-alpha, HSP-60, anti-HSP-60 antibodies, and anti-sperm antibodies.. Leukocytes in semen significantly correlated with an increase in IL-6, IL-8, and TNF-alpha. The simultaneous presence of pathogens and leukocytes was associated with high levels of IL-8 and TNF-alpha, whereas IL-6 was more associated with the presence of leukocytes. Anti-HSP-60 antibodies positively correlated with IL-6 and IL-8. The presence of anti-sperm antibodies highly associated with an increase in anti-HSP-60 antibodies.. The type of cytokines present in the semen will depend on the single or simultaneous presence of leukocytes and/or pathogens. Chronic male genital tract infections could be associated with the development of anti-HSP-60 antibodies and anti-sperm antibodies.

Topics: Adult; Antibodies; Chaperonin 60; Chlamydia Infections; Chlamydia trachomatis; Cytokines; Humans; Infertility, Male; Interleukin-10; Interleukin-6; Interleukin-8; Leukocytes; Male; Middle Aged; Spermatozoa; Tumor Necrosis Factor-alpha; Venezuela

To determine the signaling pathway required for Chlamydial induction of IL-8 expression in epithelial cells.. The production and localization of IL-8 in Chlamydia-infected Hela 229 cells were monitored using Western blot, immunoflourescence, and ELISA. Activation of MAPK and NF-kappaB signaling pathways were detected by Western blot and immunoflourescence. The effect of different signaling pathways on Chlamydia-induced Il-8 was measured by experiments of chemical inhibitors.. IL-8 was induced by Chlamydia and was time-dependant. Chlamydial infection activated MAPK/ERK and MAPK/p38 pathways but not NF-kappaB pathway. Chlamydial induction of IL-8 was blocked by small molecule inhibitors targeting the ERK and p38 pathways.. Chlamydia-induced IL-8 in cervical epithelial cells, the natural target cell type of Chlamydia trachomatis infection, is dependent on MAPK pathway but not NF-kappaB pathway, which provides important information for further understanding the molecular mechanism of Chlamydia-induced inflammatory pathologies.

Topics: Chlamydia Infections; Chlamydia trachomatis; Epithelial Cells; HeLa Cells; Humans; Interleukin-8; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Signal Transduction

Chlamydiae are obligate intracellular bacteria that frequently cause human disease. Chlamydiae replicate in a membranous vacuole in the cytoplasm termed inclusion but have the ability to transport proteins into the host cell cytosol. Chlamydial replication is associated with numerous changes of host cell functions, and these changes are often linked to proteolytic events. It has been shown earlier that the member of the NF-κB family of inflammation-associated transcription factors, p65/RelA, is cleaved during chlamydial infection, and a chlamydial protease has been implicated. We here provide evidence that the chlamydial protease chlamydial protease-like activity factor (CPAF) is responsible for degradation of p65/RelA during infection. This degradation was seen in human and in mouse cells infected with either Chlamydia trachomatis or Chlamydia pneumoniae where it correlated with the expression of CPAF and CPAF activity. Isolated expression of active C. trachomatis or C. pneumoniae CPAF in human or mouse cells yielded a p65 fragment of indistinguishable size from the one generated during infection. Expression of active CPAF in human cells caused a mild reduction in IκBα phosphorylation but a strong reduction in NF-κB reporter activity in response to interleukin-1β. Infection with C. trachomatis likewise reduced this responsiveness. IL-1β-dependent secretion of IL-8 was further reduced by CPAF expression. Secretion of CPAF is, thus, a mechanism that reduces host cell sensitivity to a proinflammatory stimulus, which may facilitate bacterial growth in vivo.

Topics: Animals; Cell Line; Chlamydia Infections; Chlamydia trachomatis; Endopeptidases; Humans; Immune System; Inflammation; Interleukin-1beta; Interleukin-8; Mice; NF-kappa B; Signal Transduction; Time Factors

Chlamydia trachomatis is a leading cause of sexually transmitted infection worldwide and responsible for myriad of immunopathological changes associated with reproductive health. Delayed secretion of proinflammatory chemokine interleukin (IL)-8 is a hallmark of chlamydial infection and is dependent on chlamydial growth. We examined the effect of iron chelators on IL-8 production in HeLa 229 (cervix epitheloid cell, CCL2) cells infected with C. trachomatis. IL-8 production was induced by Iron chelator DFO and Mimosine, however, synergy with chlamydial infection was obtained with DFO only. Temporal expression of proinflammatory secreted cytokines IL-1beta, TNF-alpha, and IL-8 did not show synchrony in Chlamydia trachomatis infected cells. Secretion of IL-8 from Hela cells infected with C. trachomatis was not dependent on IL-1 beta and TNF- alpha induction. These results indicate towards involvement of iron in chlamydia induced IL-8 production.

Topics: Chlamydia Infections; Chlamydia trachomatis; Enzyme-Linked Immunosorbent Assay; HeLa Cells; Humans; Interleukin-1beta; Interleukin-8; Iron; Iron Chelating Agents; Tumor Necrosis Factor-alpha

This study was undertaken to evaluate the gene expression profile in monocytes from three patients with reactive arthritis (ReA) in remission in order to identify candidate genes accounting for a potential susceptibility to ReA. Gene expression analyses revealed eight differentially expressed mRNA transcripts in monocytes of ReA patients. The major part of genes encoded cytokines, growth factors and chemokines. There was a remarkably high proportion of proangiogenic factors, in particular IP10, ENA-78, and IL-8 accounting for a genetically determined susceptibility to ReA at the host cell level.

Topics: Arthritis, Reactive; Case-Control Studies; Chemokine CXCL5; Chlamydia Infections; Chlamydia trachomatis; Clostridioides difficile; Enterocolitis, Pseudomembranous; Gene Expression Profiling; Genetic Predisposition to Disease; Humans; Interleukin-8; Prohibitins; Receptors, Cytokine; RNA, Messenger; Yersinia enterocolitica; Yersinia Infections

This study evaluates the role of interleukin 8 (IL-8) and anti-Chlamydia trachomatis (CT) immunoglobulin A (IgA) in total ejaculate (TE) of patients affected by chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) as potential markers in prostatic CT infection.. Seventy-eight consecutive patients with a diagnosis of CP/CPPS and CT infection were enrolled; 20 healthy volunteers represented the control group. All subjects underwent microbiologic analysis for common bacteria, yeasts, and viruses in TE, expressed prostatic secretion, and urine samples and molecular analysis for CT identification, anti-CT species-specific IgA, and IL-8 levels. Questionnaires regarding symptoms were given to each subject to determine correlations between clinical and laboratory data.. Thirty-five patients were positive for CT plasmid DNA, but none of the controls were positive. Mucosal IgA was detected in 69.2% of patients and significant levels of IL-8 were detected in 75.6% of them. Significant correlations between IL-8 and mucosal IgA (p<0.001) and between IL-8 levels and symptom score results (p<0.001) were found. IL-8 values strongly correlated with CP/CPPS (p<0.001). Moreover, the patients with higher levels of IL-8 and higher positivity for IgA reported the worst symptoms.. Our results clearly highlight the role of immune system activation in the pathophysiology of CP/CPPS and that seminal IL-8 and mucosal IgA levels specific to CT antigens appear to be the best immunologic markers of chronic chlamydial prostatitis status.

Topics: Adult; Antibodies, Bacterial; Chlamydia Infections; Chlamydia trachomatis; Chronic Disease; Humans; Immunoglobulin A, Secretory; Interleukin-8; Male; Middle Aged; Pelvic Pain; Prostatitis; Semen

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

Chlamydia trachomatis infection is associated with severe Fallopian tube tissue damage leading to tubal infertility and ectopic pregnancy. To explore the molecular mechanisms behind infection an ex vivo model was established from human Fallopian tubes and examined by scanning electron microscopy and immunohistochemistry. Extensive tissue destruction affecting especially ciliated cells was observed in C. trachomatis infected human Fallopian tube organ culture. Interleukin-1 (IL-1) produced by epithelial cells was detected after infection. Addition of IL-1 receptor antagonist (IL-1RA) completely eliminated tissue destruction induced by C. trachomatis. The anti-inflammatory cytokine IL-10 reduced the damaging effect of C. trachomatis infection, however, to a lesser extent than IL-1RA. Furthermore, IL-1 was found to induce IL-8, a neutrophil attractant, using a signal transduction pathway involving p38 MAP kinase. Consequently, IL-1 has the potential to generate a cellular infiltrate at the site of infection in vivo. Blocking the IL-1 receptors by IL-1RA eliminated tissue destruction and cytokine production. Hence, these studies show the importance of IL-1 in initiating the tissue destruction observed in the Fallopian tube following C. trachomatis infection. Because leukocytes are absent in the ex vivo model, this study strongly indicates that IL-1 is the initial proinflammatory cytokine activated by C. trachomatis infection.

Topics: Chlamydia Infections; Chlamydia trachomatis; Epithelial Cells; Fallopian Tubes; Female; Humans; Immunohistochemistry; Interleukin-1; Interleukin-10; Interleukin-8; Microscopy, Electron, Scanning; Organ Culture Techniques; Receptors, Interleukin-1

Although much has been reported on the in vitro interaction of Chlamydia trachomatis with cells derived from the female genital tract, little is known of its interaction with male genital tract epithelium. The aim of this work was to investigate the effect of C. trachomatis serovar E on immortalized normal human urethral epithelial cells and on immortalized normal adult human prostate epithelial cells with regard to chlamydial growth and secretion of cytokines. After infection, these epithelial cells were assessed for their support of chlamydial growth in comparison with HeLa cells, and cytokine levels in cell culture supernatants were determined by ELISA. Although the male-derived epithelial cells supported growth of chlamydiae, the best growth was seen in HeLa cells. In contrast to prostate epithelial cells, the urethral epithelial cells released much larger quantities of interleukin 1alpha (IL-1alpha) following infection, whereas both IL-6 and IL-8 were produced in larger quantities by infected prostate cells. At 7 days post-infection, HeLa cells consistently produced large quantities of all three cytokines. In conclusion, the male-derived cell lines were shown to support the invasion of C. trachomatis and initiate a proinflammatory response to infection. From in vitro studies the suggestion that high levels of IL-6 could be a possible marker for chlamydial prostatitis is confirmed. Although not as marked a change, it is also suggested that higher IL-8 levels could be associated more with infection of the prostate than the urethra. Differential cytokine production by different male-derived epithelial cells could help determine the site of chlamydial infection and help in the study of pathogenesis.

Topics: Biomarkers; Cell Line; Chlamydia Infections; Chlamydia trachomatis; Culture Media, Conditioned; Cytokines; Epithelial Cells; Female; Humans; Interleukin-1alpha; Interleukin-6; Interleukin-8; Male; Organ Specificity; Prostate; Time Factors; Urethra; Virulence

Diseases associated with Chlamydia infection, such as pelvic inflammatory disease and ectopic pregnancy, are due to inflammation-mediated tissue damage and scarring that occur after chronic or repeated infections. The inflammatory chemokine interleukin-8 (IL-8) is produced by Chlamydia-infected cells through an endogenous mechanism of activation, independent of soluble factors in the supernatant. The host signaling pathways necessary for this response are not understood, but the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) has been shown to be activated at similar times as IL-8 mRNA up-regulation. The purpose of this study was to elucidate the MAPK pathways necessary to induce the endogenous IL-8 response to Chlamydia trachomatis infection of epithelial cells. IL-8 induced by infection with C. trachomatis L2 was shown to be dependent on ERK and independent of p38 and Jun N-terminal MAPK by use of chemical inhibitors of the signaling pathways. Persistent ERK activation during IL-8 mRNA production at 24 h postinfection was necessary to maintain the response. C. trachomatis serovar D also induced IL-8 in an ERK-dependent manner. We concluded that IL-8 induced during infection of epithelial cells is dependent on continual activation of ERK by C. trachomatis.

Topics: Animals; Cell Line; Chlamydia Infections; Chlamydia trachomatis; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; HeLa Cells; Humans; Interleukin-8; MAP Kinase Signaling System; Mice

Chlamydia trachomatis, an intracellular obligate bacterium, remains responsible for a large spectrum of disorders that can progress to chronic diseases, resulting in severe sequelae, such as tubal infertility and blindness. These sequelae may be due to deleterious immune responses induced by repeated or persistent infections. By initiating and regulating inflammation as well as immune responses, pro-inflammatory cytokines secreted by local infected epithelial and immune cells, such as monocytes, may play an essential role in immunity and in the immunopathogenesis of chlamydial diseases. In this study, we mimicked the in vivo interaction between epithelial cells and monocytes by co-culturing epithelial-like HeLa cells with monocyte-like THP-1 cells. Pro-inflammatory cytokines [interleukin-beta (IL-1beta), IL-6, IL-8, IL-10, IL-12p70 and tumour necrosis factor-alpha (TNF-alpha)] were measured by multiplexed cytometric bead array assay over a period of 18 days. We observed that pro-inflammatory cytokine secretion was augmented after C. trachomatis infection in HeLa and THP-1 cells. However, this heightened secretion was subsequently reduced. When infected HeLa cells were co-cultured with THP-1 cells, IL-6 and IL-8 secretion was sustained, IL-1beta expression followed a bell-shaped curve and IL-10, IL-12p70 and TNF-alpha synthesis was down regulated. IL-6 and IL-8 may be involved in the immunopathogenesis of chronic chlamydial infections. We also observed that throughout C. trachomatis persistence induced by doxycycline (Dox) treatment, IL-1beta, IL-6, IL-8 and TNF-alpha expression was reduced, whereas the synthesis of IL-10 and IL-12p70 remained unchanged but not sustained. Thus, during chlamydial persistence infection evoked by treatment with Dox, none of the tested cytokines showed sustained expression.

Topics: Cell Line; Cell Survival; Chlamydia Infections; Chlamydia trachomatis; Coculture Techniques; Doxycycline; Gene Expression; HeLa Cells; Humans; Interleukin-6; Interleukin-8; Time Factors; Tumor Necrosis Factor-alpha

Topics: Aza Compounds; Cell Line; Cell Movement; Chemokine CCL2; Chlamydia Infections; Chlamydophila pneumoniae; Endothelium, Vascular; Fluoroquinolones; Gatifloxacin; Humans; Interleukin-8; Monocytes; Moxifloxacin; Neutrophils; Ofloxacin; Phagocytosis; Quinolines; Stimulation, Chemical; Tumor Necrosis Factor-alpha

Chlamydia pneumoniae infection of lymphocytes in blood has been documented, and it is apparent that control of this pathogen in lymphocytes as well as immune functions of the infected lymphocytes may be critical in the development of chronic inflammatory diseases associated with infection by this bacterium. Since immune function of lymphocytes infected with C. pneumoniae has not been well studied, the cytokine response of lymphocytes infected with this pathogen was analyzed using an in vitro infection model of the Molt-4 human lymphoid cell line. C. pneumoniae infection of the cells showed a persistent infection without any vigorous growth of the bacteria. Analysis of the cytokine response of the cells persistently infected with C. pneumoniae showed minimum induction of inflammatory cytokine TNF-alpha message, determined by real-time reverse transcription (RT)-PCR in the lymphocytes, even though the infection of THP-1 monocytic cells showed a marked induction of this cytokine messages. BIC (a lymphocyte activation marker gene) as well as IFN-gamma messages were also minimally induced by the infection in Molt-4 lymphocytes. In contrast, constitutive expression of interleukin 8 (IL-8) messages of Molt-4 cells was suppressed by the infection. Thus, these results suggest that lymphocytes persistently infected with C. pneumoniae may have attenuated cytokine responses.

Topics: Chlamydia Infections; Chlamydophila pneumoniae; Humans; Inclusion Bodies; Interferon-gamma; Interleukin-8; Lymphocyte Activation; Microscopy, Fluorescence; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Ribosomal, 16S; T-Lymphocytes; Tumor Necrosis Factor-alpha

The probable risk factors leading to aortic valve calcification are not clearly defined. The cross-sectional study of 85 patients with vascular and valvular calcification was performed. Correlations between the immune tests and aortic stenosis severity were investigated. The predictors of aortic valve calcification were probably C-reactive protein and interleukin-6. The predictors of aortic stenosis progression were interleukin-8, antibodies of Chlamydia pneumoniae and cytomegalovirus, and dysregulation of complement's components. Implication of immune reactivity could influence aortic valve calcification.

Topics: Aged; Aged, 80 and over; Antibodies, Bacterial; Antibodies, Viral; Aortic Valve Stenosis; C-Reactive Protein; Calcinosis; Chlamydia Infections; Chlamydophila pneumoniae; Cross-Sectional Studies; Cytomegalovirus; Cytomegalovirus Infections; Disease Progression; Humans; Interleukin-6; Interleukin-8; Male; Risk Factors; Russia

The lipopolysaccharide (LPS) of Chlamydia trachomatis serotype E was isolated from tissue culture-grown elementary bodies and analyzed structurally by mass spectrometry and 1H, 13C and 31P nuclear magnetic resonance. The LPS is composed of the same pentasaccharide bisphosphate alphaKdo-(2-8)-alphaKdo-(2-4)-alphaKdo-(2-6)-betaGlcN-4P-(1-6)-alphaGlcN-1P (Kdo is 3-deoxy-alpha-d-manno-oct-2-ulosonic acid) as reported for C. trachomatis serotype L2[Rund, S., Lindner, B., Brade, H. and Holst, O. (1999) J. Biol. Chem. 274, 16819-16824]. The glucosamine disaccharide backbone is substituted with a complex mixture of fatty acids with ester or amide linkage whereby no ester-linked hydroxy fatty acids were found. The LPS was purified carefully (with contaminations by protein or nucleic acids below 0.3%) and tested for its ability to induce proinflammatory cytokines in several readout systems in comparison to LPS from C. trachomatis serotype L2 and Chlamydophila psittaci strain 6BC as well as enterobacterial smooth and rough LPS and synthetic hexaacyl lipid A. The chlamydial LPS were at least 10 times less active than typical endotoxins; specificity of the activities was confirmed by inhibition with the LPS antagonist, B1233, or with monoclonal antibodies against chlamydial LPS. Like other LPS, the chlamydial LPS used toll-like receptor TLR4 for signalling, but unlike other LPS activation was strictly CD14-dependent.

Topics: Animals; Antibodies, Monoclonal; Chlamydia Infections; Chlamydia trachomatis; Chlamydophila psittaci; CHO Cells; Cricetinae; Drosophila Proteins; Electrophoresis, Polyacrylamide Gel; Fatty Acids; Flow Cytometry; Humans; Interleukin-8; Leukocytes, Mononuclear; Lipopolysaccharide Receptors; Lipopolysaccharides; Membrane Glycoproteins; NF-kappa B; Nuclear Magnetic Resonance, Biomolecular; Receptors, Cell Surface; Serotyping; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Toll-Like Receptor 4; Toll-Like Receptors; Transfection

Balanced secretion of pro- and anti-inflammatory cytokines is essential in limiting pulmonary inflammation in respiratory infections. It was hypothesised that, in acute infection with Chlamydia pneumoniae, mononuclear cells from chronic obstructive pulmonary disease (COPD) patients lack the opportunity to compensate for the inflammatory immune response by secreting adequate amounts of anti-inflammatory cytokines. Alveolar macrophages (AMs) and peripheral blood mononuclear cells (PBMCs) from eight COPD patients and eight healthy controls were infected with C. pneumoniae in order to determine interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1RA) and IL-8 expression and messenger ribonucleic acid levels. Secretion of IL-1beta was significantly enhanced in AMs (six-fold) and PBMCs (four-fold) from COPD patients after infection with C. pneumoniae. Compared to the control group, release of its anti-inflammatory counterpart IL-1RA was diminished in COPD patients, resulting in a significantly higher IL-1beta/IL-1RA ratio in C. pneumoniae-infected AMs and PBMCs from COPD patients. Mononuclear cells from chronic obstructive pulmonary disease patients have less capacity for balancing the pro-inflammatory immune response caused by Chlamydia pneumoniae infection than those from healthy controls. These findings suggest that, during acute exacerbation with intracellular pathogens, chronic obstructive pulmonary disease patients are predisposed to inflammatory changes in the lungs.

Topics: Adult; Aged; Chlamydia Infections; Chlamydophila pneumoniae; Humans; In Vitro Techniques; Interleukin-1; Interleukin-8; Leukocytes, Mononuclear; Macrophages, Alveolar; Middle Aged; Pneumonia, Bacterial; Pulmonary Disease, Chronic Obstructive; Receptors, Interleukin-1; RNA, Messenger

Inflammatory mediators are involved in activation of the coagulation system, and elevated plasma concentrations of IL-6 and IL-8 are associated with an increased risk of venous thrombosis. Using serologic and molecular biologic tests, we investigated in a case-control study on patients with recurrent venous thrombosis the association between Chlamydia (C) pneumoniae and venous thrombosis and we evaluated the relation between C. pneumoniae serology and the cytokines IL-6 and IL-8. The presence of C. pneumoniae antibody titers > or = 1:16 was not associated with an increased risk of venous thrombosis (odds ratio 0.8 95% CI, 0.4-1.7). Circulating C. pneumoniae-DNA was detected in only one patient and two control subjects. IgG antibody titers against C. pneumoniae were not correlated with the concentrations of IL-6 and IL-8. These results indicate that the inflammatory process shown in patients with venous thrombosis is not related to C. pneumoniae.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Case-Control Studies; Chlamydia Infections; Chlamydophila pneumoniae; Female; Humans; Immunoglobulin G; Immunologic Tests; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Seroepidemiologic Studies; Venous Thrombosis

Persistent infection with Chlamydia pneumoniae (Chlamydophila pneumoniae) has been implicated in the development of atherosclerosis, asthma and other chronic diseases. However, data on treatment of C. pneumoniae infections are limited. Microbiological failure of antimicrobial therapy has been described, even after prolonged courses of treatment with azithromycin, doxycycline and erythromycin. Gemifloxacin is an enhanced-affinity fluoroquinolone with excellent activity against most common respiratory pathogens, including C. pneumoniae. The effect of prolonged treatment with gemifloxacin, compared with azithromycin, on viability of C. pneumoniae was investigated in a continuous infection model. Gemifloxacin at final con-centrations of 0.25 and 2.5 mg/L reduced the viability of C. pneumoniae by 5 log(10), which was similar to the effect of azithromycin. However, both antimicrobials failed to completely eliminate C. pneumoniae from continuously infected cells, even after 30 days of treatment. Both antibiotics decreased levels of interleukin-6 and interleukin-8 in this model, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cells, Cultured; Chlamydia Infections; Chlamydophila pneumoniae; Cytokines; Fluoroquinolones; Gemifloxacin; Humans; Interleukin-12; Interleukin-6; Interleukin-8; Naphthyridines

Penile urethral swabs collected from PCR-confirmed Chlamydia trachomatis-infected, C. trachomatis-uninfected, and non-C. trachomatis-infected, nongonococcal urethritis-infected males were analyzed for cytokine, total immunoglobulin (Ig), and specific antibody levels by enzyme-linked immunosorbent assay. Differential cellular components of the swab transport medium were also enumerated for the same groups. Although low, the levels of C. trachomatis-specific IgA and IgG antibodies and interleukin 8 cytokine were significantly higher in C. trachomatis-infected individuals. There were no significant differences in the levels of seven additional cytokines evaluated.

Topics: Adolescent; Adult; Antibodies, Bacterial; Chlamydia Infections; Chlamydia trachomatis; Cytokines; Humans; Immunoglobulin A; Immunoglobulins; Interleukin-8; Lymphocyte Count; Male; Middle Aged; Proteinase Inhibitory Proteins, Secretory; Proteins; Th1 Cells; Th2 Cells; Urethra; Urethral Diseases

We detected levels of interleukin-8(IL-8) and nitric oxide(NO) in 62 prostatic fluids. The results were that microbiologic exam, IL-8 content, and NO level in control group were all negative; there was not significant difference on the microbiologic exam and NO level between the chronic prostatitis group and non-prostatitis group; there was significant difference between two groups of IL-8 positive ratio. These results suggest that the IL-8 detected in the prostatic fluid of patients with prostatitis may be a diagnostic indicator of prostatic infection.

Topics: Adult; Chlamydia Infections; Chlamydia trachomatis; Chronic Disease; Humans; Interleukin-8; Male; Middle Aged; Nitric Oxide; Prostatitis; Ureaplasma Infections; Ureaplasma urealyticum

Chlamydia species infect epithelial cells at mucosal surfaces, and are major causes of sexually transmitted diseases. Infection is characterized by inflammation which is exacerbated upon reinfection, ultimately leading to tissue damage and scarring. Although central for the development of disease manifestations, little is known about the mechanisms that initiate and sustain the inflammatory response to Chlamydia. Infection of cervical and colonic epithelial cells with Chlamydia trachomatis and Chlamydia psittaci is shown in the present studies to upregulate mRNA expression and secretion of the proinflammatory cytokines IL-8, GRO alpha, GM-CSF, and IL-6. In contrast to the rapid, but transient, cytokine induction following infection with other invasive bacteria, the epithelial cytokine response to Chlamydia was delayed until 20-24 h after infection, persisted throughout the chlamydial growth cycle (2-4 d), and required bacterial protein synthesis. Moreover, epithelial cell lines and primary endocervical epithelial cells released IL-1alpha after Chlamydia infection, and increased secretion of the proinflammatory cytokines could be inhibited by anti-IL-1alpha. This suggests that IL-1alpha, released following lysis of infected epithelial cells, may amplify the inflammatory response by stimulating additional cytokine production by noninfected neighboring cells. These findings suggest a novel pathophysiologic concept wherein the acute host response to Chlamydia at mucosal surfaces is primarily initiated and sustained by epithelial cells, the first and major targets of chlamydial infection.

Topics: Actins; Bacterial Proteins; Cells, Cultured; Chemokine CXCL1; Chemokines, CXC; Chemotactic Factors; Chlamydia Infections; Chlamydia trachomatis; Chlamydophila psittaci; Epithelial Cells; Epithelium; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; HeLa Cells; Humans; Immunity, Mucosal; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-1; Interleukin-6; Interleukin-8; Polymerase Chain Reaction; Polysaccharides, Bacterial; RNA, Messenger; Time Factors; Transcription, Genetic; Transforming Growth Factor beta

The role of cytokines in the pathogenesis of pneumonia is still poorly understood. In a previous study the diagnostic value of measuring blood concentrations of interleukin 6 and interferon gamma was established. In the present study the value of blood concentrations of interleukin 8, granulocyte-colony stimulating factor, and lactoferrin as markers of bacteraemic pneumonia is evaluated.. The circulating concentrations of interleukin 8 (IL-8), granulocyte-colony stimulating factor (G-CSF), and lactoferrin were measured in 14 patients with bacteraemic pneumococcal pneumonia and 49 patients with atypical pneumonia or influenza A infection using enzyme immunoassays.. Serum G-CSF concentrations were higher in the group with bacteraemic pneumococcal pneumonia, and G-CSF values correlated with the white blood cell count and levels of C-reactive protein (CRP). The levels of IL-8 were higher in the group with bacteraemic pneumococcal pneumonia than the groups with Chlamydia pneumonia, Legionella pneumonia, or influenza A infection, but there was no difference when compared with the group with Mycoplasma pneumonia. A white blood cell count of > 15 x 10(9)/l was highly suggestive of bacteraemic pneumonia. The concentrations of lactoferrin were raised in all groups except those with influenza A infection, but no difference was found between the different aetiological groups. A correlation was found between lactoferrin and white blood cell counts.. Serum G-CSF and IL-8 concentrations are potential markers of bacteraemic pneumonia.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Biomarkers; Chlamydia Infections; Cytokines; Female; Granulocyte Colony-Stimulating Factor; Humans; Influenza A virus; Influenza, Human; Interleukin-8; Lactoferrin; Legionnaires' Disease; Leukocyte Count; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Pneumonia, Pneumococcal