Toll-like Receptors And Inflammatory Factors And Pleural Disease Relationship

Part one: Soluble Toll-Like Receptors in Pleural EffusionsBackground: The aim of this study was to investigate the presence of toll-like receptors (TLRs) in pleural effusions, and the diagnostic values of TLRs for pleural effusion with various etiologies.Methods: Pleural effusion and serum samples were collected from 102 patients (36 with malignant pleural effusion, 36 with tuberculous pleural effusion, 18 with bacterial pleural effusion, and 12 with transudative pleural effusion). The concentrations of TLR1 to TLR10 were determined in effusion and serum samples by enzyme linked immunosorbent assay.Results: The concentrations of TLR1, TLR3, TLR4, TLR7 and TLR9 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups; The levels of many TLRs in pleural effusion were positively correlated. ROC curve analysis revealed that optimal differentiation between bacterial and non-bacterial PE could be achieved with cutoff points of 1.40 ng/ml for TLR1 (area under the curve = 0.831; sensitivity = 93.3.6%; specificity = 62.7%);≥1.05 ng/ml for TLR3 (area under the curve = 0.843; sensitivity = 73.3%; specificity = 87.1%);≥1.26 ng/ml for TLR4 (area under the curve = 0.842; sensitivity = 66.7%; specificity = 95.2%);≥24.08 ng/ml for TLR7 (area under the curve = 0.883; sensitivity = 80.0%; specificity = 87.1%) and≥14.77 ng/ml for TLR9 (area under the curve = 0.786; sensitivity = 80.0%; specificity = 82.3%). Conclusions: The concentrations of TLR1, TLR3, TLR4, TLR7 and TLR9 appeared to be increased in bacterial pleural effusion compared to non-bacterial pleural effusions. Determination of these pleural TLRs may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies.Part two: Assoeiation between Toll-like receptor-4 gene polymorphism and tuberculous pleuritisObjective:To investigate the occurrence of the Asp299Gly and Thr399Ile polymorphism of the Toll-like receptor 4 (TLR4) gene in patients with tuberculosis,tuberculous pleuritis and healthy controles.Methods: TLR4 gene Asp299Gly allele and Thr399Ile allele mutation were surveyed by mispairing polymerase chain reaetion-restrieted fragment length polymorphism (PCR- RFLP) analysis technique in 185 tuberculous pantients (including 68 tuberculous pleuritis patients) and 110 healthy volunteers.Results: No mutation of TLR4 gene Asp299Gly allele and Thr399Ile allele were detected in all 295 DNA samples.Conclusion: The non-synonymous single nucleotide polymorphism Asp299Gly and and Thr399Ile in TLR4 gene was rare and was not assoeiated with tuberculosis and tuberculous pleuritis in Chinese Population in Guangxi Provinee.Part three: Soluble CD14, CXCL9/MIG and CXCL10/IP-10 in pleural effusionsObjective:To investigate the expression and cooperation of the sCD14, CXCL9/MIG and CXCL10/IP-10 in pleural effusions of various causes,and the diagnostic values of these factors for pleural effusion with various etiologies.Methods: Pleural effusion and serum samples were collected from 88 patients who presented to the respiratory institute (30 with malignant pleural effusion, 32 with tuberculous pleural effusion, 15 with bacterial pleural effusion, and 11 with transudative pleural effusion). The concentrations of sCD14, MIG and IP-10 were determined in effusion and serum samples by enzyme linked immunosorbent assay (ELISA).Results: In tuberculous pleural effusion, the concentration of sCD14 were significantly higher than those in malignant, bacterial, and transudative groups(p<0.05); The level of MIG were significantly higher than those in malignant and transudative groups(p<0.01); and the concentration of IP-10 were significantly higher than those in bacterial and transudative groups(p<0.01). The concentrations of sCD14, MIG and IP-10 in tuberculous pleural effusions were significantly higher than those in non-tuberculous pleural effusions(p<0.01). Analysis of ROC curves revealed that sCD14 and IP-10 appear good sensitivity(90.3%, 77.4%), and MIG has the specificity as 89.3%. In pleural effusion, IP-10 levels were positively correlated with levels of sCD14(r = 0.551, p<0.001) and MIG(r = 0.593, p<0.001).Conclusions: sCD14, MIG and IP-10 may contribute to the process of immune response against MTB during pleural inflammation. Determination of these inflammatory facors may improve the ability of clinicians to differentiate pleural effusion patients of tuberculous origin from those with other etiologies.