In infertile women, cells from Chlamydia trachomatis infected site release higher levels of interferon-gamma, interleukin-10 and tumor necrosis factor-alpha upon heat shock protein stimulation than fertile women

<p>Abstract</p> <p>Background</p> <p>The magnitude of reproductive morbidity associated with sexually transmitted Chlamydia trachomatis infection is enormous. Association of antibodies to chlamydial heat shock proteins (cHSP) 60 and 10 with various disease sequelae such as infertility or ectopic pregnancy has been reported. Cell-mediated immunity is essential in resolution and in protection to Chlamydia as well as is involved in the immunopathogenesis of chlamydial diseases. To date only peripheral cell mediated immune responses have been evaluated for cHSP60. These studies suggest cHSPs as important factors involved in immunopathological condition associated with infection. Hence study of specific cytokine responses of mononuclear cells from the infectious site to cHSP60 and cHSP10 may elucidate their actual role in the cause of immunopathogenesis and the disease outcome.</p> <p>Methods</p> <p>Female patients (n = 368) attending the gynecology out patient department of Safdarjung hospital, New Delhi were enrolled for the study and were clinically characterized into two groups; chlamydia positive fertile women (n = 63) and chlamydia positive infertile women (n = 70). Uninfected healthy women with no infertility problem were enrolled as controls (n = 39). cHSP60 and cHSP10 specific cytokine responses (Interferon (IFN)-gamma, Interleukin (IL)-10, Tumor Necrosis Factor (TNF)-alpha, IL-13 and IL-4) were assessed by ELISA in stimulated cervical mononuclear cell supernatants.</p> <p>Results</p> <p>cHSP60 and cHSP10 stimulation results in significant increase in IFN-gamma (P = 0.006 and P = 0.04 respectively) and IL-10 levels (P = 0.04) in infertile group as compared to fertile group. A significant cHSP60 specific increase in TNF-alpha levels (P = 0.0008) was observed in infertile group as compared to fertile group. cHSP60 and cHSP10 specific IFN-gamma and IL-10 levels were significantly correlated (P < 0.0001, r = 0.54 and P = 0.004, r = 0.33 respectively) in infertile group.</p> <p>Conclusion</p> <p>Our results suggest that exposure to chlamydial heat shock proteins (cHSP60 and cHSP10) could significantly affect mucosal immune function by increasing the release of IFN-gamma, IL-10 and TNF-alpha by cervical mononuclear cells.</p

Diagnostic value of anti-cyclic citrullinated peptides and association with HLA-DRB1 shared epitope alleles in African rheumatoid arthritis patients

INTRODUCTION: The purpose of this study was to examine the diagnostic performance of autoantibodies against citrullinated peptides/proteins (ACPA) and to determine the prevalence of HLA-DRB1 shared epitope alleles (SE) in African patients with rheumatoid arthritis (RA). METHODS: Serum levels of anti-cyclic citrullinated peptides antibodies (anti-CCP2, anti-CCP3), IgM and IgA rheumatoid factors (RF) were measured by enzyme-linked immunosorbent assay in the serum of 56 consecutive RA patients regularly followed in the Rheumatology Unit of the School of Medicine, University of Yaounde, Yaounde, Cameroon. Genotyping of HLA-DRB1 alleles was performed by polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes on microbeads arrays. Fifty-one patients with other inflammatory rheumatic diseases and 50 healthy individuals were included as controls. RESULTS: An anti-CCP2 assay showed the best diagnosis sensitivity (82%) and specificity (98%) with high positive predictive (PPV) (96%) and negative predictive values (NPV) (91%). Thirty percent of RA patients were carrying at least one copy of the HLA-DRB1 shared epitope (SE) compared to 10% and 14% of patients with other inflammatory rheumatic diseases and healthy individuals, respectively. The presence of the SE was associated with the production of ACPA. CONCLUSIONS: Anti-CCP2 antibodies are useful markers of RA in African patients. In this cohort, the prevalence of the SE is higher in RA patients than in controls but lower than that reported in patient cohorts of European ancestry. The discrepancy between the high prevalence of ACPA-positive patients and the relatively low number of SE-positive cases suggest that, in addition to SE, other genetic factors control the development of ACPA in African RA patients

Adipokines correlate with pain in lower limb osteoarthritis: different associations in hip and knee

Purpose: Our aim was to investigate whether serum and synovial-fluid (SF) concentrations of interleukin-6 (IL-6), leptin, adiponectin, resistin or visfatin are associated with joint pain in hip and knee in end-stage osteoarthritis (OA). Methods: A cross-sectional study assessing patients with hip and knee OA undergoing total joint arthroplasty between January and December 2010 was conducted at a large university hospital. Serum and SF cytokine and adipokine concentrations were determined in samples obtained on the day of surgery. The main outcome was pain severity measured pre-operatively using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS) pain scores. Results: A total of 206 patients were involved (112 with hip and 94 with knee OA). Median age was 72years [interquartile range (IQR) 66-79], 59% were women. All adipokine levels were significantly higher in the SF of hip joints than in that of knee joints, except for leptin, which tended to be higher in the knee. In both hip and knee OA, median serum concentrations of leptin, adiponectin, resistin and visfatin exceeded those in SF, whereas for IL-6, median concentrations were much higher in SF than in serum. In hip OA, worse pain was significantly associated with high SF concentrations of IL-6, visfatin and leptin; in knee OA, it was associated with high SF leptin and low SF adiponectin concentrations and a low adiponectin-leptin ratio. Conclusion: Our findings support a connection between intra-articular concentrations of several adipokines and severity of preoperative OA pain. However, the specific adipokines differed by joints: in hip OA, pain was associated with IL-6 and visfatin and in knee OA with adiponectin; leptin played a role in both hip and knee OA

The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes

Six novel members of the IL-1 family of cytokines were recently identified, primarily through the use of DNA database searches for IL-1 homologues, and were named IL-1F5 to IL-1F10. In the present study, we investigated the effect of IL-1F8 on primary human joint cells, and examined the expression of the new IL-1 family members in human and mouse joints. Human synovial fibroblasts (hSFs) and human articular chondrocytes (hACs) expressed the IL-1F8 receptor (IL-1Rrp2) and produced pro-inflammatory mediators in response to recombinant IL-1F8. IL-1F8 mRNA expression was increased in hSFs upon stimulation with proinflammatory cytokines, whereas in hACs IL-1F8 mRNA expression was constitutive. However, IL-1F8 protein was undetectable in hSF and hAC culture supernatants. Furthermore, although IL-1β protein levels were increased in inflamed human and mouse joint tissue, IL-1F8 protein levels were not. IL-1F8 levels in synovial fluids were similar to or lower than those in matched serum samples, suggesting that the joint itself is not a major source of IL-1F8. Serum levels of IL-1F8 were similar in healthy donors, and patients with rheumatoid arthritis, osteoarthritis and septic shock, and did not correlate with inflammatory status. Interestingly however, we observed high IL-1F8 levels in several serum samples in all groups. In conclusion, IL-1F8 exerts proinflammatory effects in primary human joint cells. Joint and serum IL-1F8 protein levels did not correlate with inflammation, but they were high in some human serum samples tested, including samples from patients with rheumatoid arthritis. It remains to be determined whether circulating IL-1F8 can contribute to joint inflammation in rheumatoid arthritis

Do synovial leptin levels correlate with pain in end stage arthritis?

Purpose: We evaluated whether synovial fluid (SF) leptin concentrations correlate with pain severity in patients with hip or knee endstage osteoarthritis (OA) and whether they mediate the association between increased joint pain and (1) female gender and (2) obesity. Methods: We conducted a cross-sectional study including patients with primary hip and knee OA undergoing joint replacement between January and December 2010. SF leptin concentrations obtained on the day of surgery were assessed. Main outcome was pain severity measured pre-operatively using WOMAC and VAS pain scales. Results: A total of 219 patients were included, 123 hip and 96 knee arthroplasties. Mean age was 72years, 59% were women. Mean SF leptin levels were 22.9 (±25.6) ng/ml in women and 5.4 (±5.9) ng/ml in men. Levels >19.6ng/ml (highest quartile) were significantly associated with increased pain on both WOMAC (mean difference −9.6, 95% CI −15.1 to −4.0) and VAS scale (mean difference 0.8, 95% CI 0.2-1.3). Associations remained unchanged after adjusting for age, co-morbidities, contra-lateral arthritic joint, OA site, and disability. The associations observed between increased pain and female gender or obesity were substantially reduced after adjusting for SF leptin. Conclusion: Joint pain is associated with SF leptin concentrations. Increased pre-operative pain observed in women and obese may be related to high intra-articular leptin level

Serum lipoproteins attenuate macrophage activation and Toll-Like Receptor stimulation by bacterial lipoproteins

Abstract Background Chlamydia trachomatis was previously shown to express a lipoprotein, the macrophage infectivity potentiator (Mip), exposed at the bacterial surface, and able to stimulate human primary monocytes/macrophages through Toll Like Receptor (TLR)2/TLR1/TLR6, and CD14. In PMA-differentiated THP-1 cells the proinflammatory activity of Mip was significantly higher in the absence than in the presence of serum. The present study aims to investigate the ability of different serum factors to attenuate Mip proinflammatory activity in PMA-differentiated THP-1 cells and in primary human differentiated macrophages. The study was also extend to another lipoprotein, the Borrelia burgdorferi outer surface protein (Osp)A. The proinflammatory activity was studied through Tumor Necrosis Factor alpha (TNF-α) and Interleukin (IL)-8 release. Finally, TLR1/2 human embryonic kidney-293 (HEK-293) transfected cells were used to test the ability of the serum factors to inhibit Mip and OspA proinflammatory activity. Results In the absence of any serum and in the presence of 10% delipidated FBS, production of Mip-induced TNF-α and IL-8 in PMA-differentiated THP-1 cells were similar whereas they were significantly decreased in the presence of 10% FBS suggesting an inhibiting role of lipids present in FBS. In the presence of 10% human serum, the concentrations of TNF-α and IL-8 were 2 to 5 times lower than in the presence of 10% FBS suggesting the presence of more potent inhibitor(s) in human serum than in FBS. Similar results were obtained in primary human differentiated macrophages. Different lipid components of human serum were then tested (total lipoproteins, HDL, LDL, VLDL, triglyceride emulsion, apolipoprotein (apo)A-I, B, E2, and E3). The most efficient inhibitors were LDL, VLDL, and apoB that reduced the mean concentration of TNF-α release in Mip-induced macrophages to 24, 20, and 2%, respectively (p Conclusions These results demonstrated the ability of serum lipids to attenuate proinflammatory activity of bacterial lipoproteins and suggested that serum lipoproteins interact with acyl chains of the lipid part of bacterial lipoproteins to render it biologically inactive.</p