Mechanism Of The Role Of Th17 Cells In The Pathogenesis Of Sepsis

Background:Th17 cells are an independent T helper cell subsets which have the feature to secrete interleukin17 (IL-17). Thl7 cells play an key role in the defense of extracellular bacterial infection, mediating chronic immune inflammation and in tumor immunity. IL-17 has a closely relationship with the infection of Klebsiella pneumonia, Citrobacter rodents, Helicobacter pylori, Salmonella, Candida albicans, hepatitis B virus and parasitic. However, in terms of the present condition of the following problems remain unsolved:1). The immune regulatory mechanisms of Th17 cells in the pathogenesis of sepsis; 2). Monocyte has the key position in the pathogenesis of sepsis, and what's the relationship between the th17 cells and Monocyte.Objective:To investigate The immune regulatory mechanisms of Th17 cells in the pathogenesis of sepsis and the relationship between Th17 cells and MonocyteMethods:the investigate was divided into four parts.Part 1:to investigate the relationship between APACHEâ…¡Score and septic patients.To collect the clinical data of the septic patients and to analysis the relationship of APACHEâ…¡score and prognosis With statistical methods.Part 2:to investigate the immune regulatory mechanisms of Th17 cells in the pathogenesis of sepsisTo divide all the septic patients into sepsis, severe sepsis and septic shock groups according to disease severity. Together with the healthy control group, the whole blood of three groups was cultured, stimulated, stained and tested by flow cytometry, then to analyze the frequency of the Th17 cells.Part 3:to investigate the immune regulatory mechanisms of Monocyte in the pathogenesis of sepsis.The blood samples of the patients and the healthy volunteers were stained then were tested by flow cytometry. To analyze the composition of the proportion of Monocyte subsets and the MFI of HLA-DR and CD14.Part 4:to investigate the relationship between Th17 cells and MonocyteThe PBMC isolated from healthy volunteer was cultured with anti-cd3, anti-cd28 and different concentrations of LPS for 3d then was stained and tested by flow cytometry.Results:Part 1:APACHEâ…¡scores of the three septic groups were significantly different (P<0.01); APACHEâ…¡score has a positive correlation with CRP, blood lactate and glucose; APACHEâ…¡score has a significantly negatively correlation with the prognosis (P<0.001).Part 2:the frequency of Th17 cells of septic patients was higher than the control group(P<0.01); Th1 cells had no significant difference; there were significant differences (P<0.01)in the frequency of Th17 cells between two groups of sepsis, severe sepsis, septic shock and healthy control except between sepsis group and severe sepsis group(P= 0.076). severe sepsis group has the highest frequency of Th17 cells among four groups and the septic shock group is has the lowest frequency; There was negatively correlation between The APACHEâ…¡score and the frequency of Th17 cells.Part 3:The Monocyte count is higher in septic patients than in healthy volunteers(P <0.05). The frequency of CD14+CD16+monocyte is significantly higher in three patient groups than in healthy control group. The MFI of HLA-DR and CD14 was significantly lower of septic patients than the healthy control's and the MFI gradually reduced with the patients' condition aggravating. Part 4:The frequency of Th17 cells of PBMC is Higher than the PBMC without LPS after 3d's culture. The frequency is 5.87% when LPS concentration was 20ng/ml which is the highest frequency between all the cultures.Conclusion:1. APACHEâ…¡score can reflect the prognosis of patients with sepsis better.2. Th17 cells play a key role in the pathogenesis of sepsis.3. Activated monocytes can promote Thl 7 response, and CD14+CD16+ monocyte play a major role in it.