The Role Of Th17/treg Cells Imbalance In The Acute Cerebral Infarction Inducing Systemic Inflammatory Response Syndrome Which Lead To Multiple Organ Dysfunction Syndrome

Objective:To observe the changes of Th17,Treg cells and related cytokines in the acute cerebral infarction(ACI)inducing systemic inflammatory response syndrome(SIRS)which lead to multiple organ dysfunction syndrome(MODS),and to explore the role of Th17/Treg cells imbalance in ACI inducing SIRS which lead to MODS,so providing an important theoretical basis for early diagnosis and treatment of ACI inducing SIRS to MODS patients.Method:139 cases from July 2015 to July 2016 in our hospital diagnosis in patients with acute cerebral infarction and complete data.According to the American College of Chest Physicians / Society of Critical Care Medicine-sponsored sepsis Diagnostic criteria for SIRS in 1991 and the Lushan Conference Diagnostic criteria for MODS in 1995,we divided into simple ACI group,ACI inducing SIRS group,ACI inducing SIRS to MODS group,the normal control group consisted of healthy persons in our hospital.All experimental group and control group were collected in early morning fasting venous blood 5ml,EDTA anticoagulation.Centrifuging Fresh blood within 2hours to obtain Serum,The changes of IL-6,IL-10,IL-17,IL-21,TGF-?,TNF-?,hs-CRP and endotoxin levels in Serum were detected by double antibody ELISA method,chemical colorimetric method,Limulus test method andautomatic immune turbidimetric assay.The remaining blood was isolated by density gradient centrifugation,and Th17 cells were detected by flow cytometry in 6-8 hours.Analysing the role of Th17/Treg cells imbalance in ACI inducing SIRS to MODS.Results:1.No statistical differences in gender,age,smoking history,hypertension,diabetes and hyperlipidemia among all groups(P > 0.05).2.The data of the proportion of CD4+CD25+FOXP3+Treg cells in total CD4+T cells in the normal control group,simple ACI group,ACI inducing SIRS group,ACI inducing SIRS to MODS group in peripheral blood were:5.48±0.43%,4.31±0.43%,2.71±0.31%,1.37±0.33%,The data of the proportion of CD4+IL-17A+Th17 cells in total CD4+T cells in the normal control group,simple ACI group,ACI inducing SIRS group,ACI inducing SIRS to MODS group in peripheral blood were:0.96±0.33 %,2.10±0.42 %,5.13±0.58 %,6.76±0.44 %.Compared with the normal control group,the proportion of CD4+CD25+FOXP3+Treg cells in total CD4+T cells in simple ACI group,ACI inducing SIRS group,ACI inducing SIRS to MODS group were all decreased(P < 0.01),the proportion of CD4+IL-17A+Th17 cells in total CD4+T cells were all increased(P <0.01).compared with the simple ACI group,the proportion of CD4+CD25+FOXP3+Treg cells in total CD4+T cells decreased significantly in ACI inducing SIRS and ACI inducing SIRS to MODS group(P < 0.01),but the proportion of CD4+CD25+FOXP3+Treg cells in total CD4+T cells was significantly higher(P < 0.01).The proportion of CD4+CD25+FOXP3+Tregcells in total CD4+T cells and the proportion of CD4+IL-17A+Th17 cells in total CD4+T cells in ACI inducing SIRS and ACI inducing SIRS to MODS group were also different(P < 0.01).3.The data of Th17 cell related cytokines TNF-?,IL-6,IL-17,IL-21 in the normal control group in peripheral blood were:11.87±2.37 pg/ml?37.32±6.39 pg/ml?16.57±4.58 pg/ml?49.11±11.27pg/ml.The data in simple ACI group were: 15.66±2.39 pg/ml ? 63.35±8.95pg/ml?55.62±11.92 pg/ml?76.23±15.31 pg/ml.The data in ACI inducing SIRS group were: 22.78±2.48 pg/ml?99.32±13.83 pg/ml?121.67±18.05 pg/ml?106.68±9.82 pg/ml.The data in ACI inducing SIRS to MODS group were:32.23±4.39 pg/ml ? 152.95±18.31 pg/ml ? 151.08±33.72 pg/ml ?121.76±6.44 pg/ml.The levels of TNF-?,IL-6,IL-17 and IL-21 in serum of simple ACI group ? ACI inducing SIRS group and ACI inducing SIRS to MODS group were higher than those in normal control group,the difference was statistically significant(P < 0.05).Compared with the simple ACI group,ACI inducing SIRS and ACI inducing SIRS to MODS are higher(P < 0.05),the difference between ACI inducing SIRS group and ACI inducing SIRS to MODS group was also statistically significant(P < 0.05).4.The data of Treg cell related cytokines IL-10,TGF-? in the normal control group in peripheral blood were: 32.94±3.18 pg/ml?415.33±49.31 pg/ml.The data in simple ACI group were:24.98±3.22 pg/ml?341.29±39.82 pg/ml.The data in ACI inducing SIRS group were:13.46±3.44 pg/ml ? 128.89±26.03 pg/ml.The data in ACI inducing SIRS to MODS group were:6.13±2.09 pg/ml?73.79±16.80 pg/ml.Thelevels of IL-10 and TGF-? in serum of simple ACI group ?ACI inducing SIRS group and ACI inducing SIRS to MODS group were lower than those in normal control group,the difference was statistically significant(P <0.05).Compared with the simple ACI group,ACI inducing SIRS and ACI inducing SIRS to MODS are lower(P < 0.05),the difference between ACI inducing SIRS group and ACI inducing SIRS to MODS group was also statistically significant(P < 0.05).5.The data of hs-CRP in the normal control group,simple ACI group,ACI inducing SIRS group,ACI inducing SIRS to MODS group in peripheral blood were: 1.59±0.20 pg/ml?15.76±4.26 pg/ml?37.66±8.45 pg/ml?44.78±7.21 pg/ml.The levels of hs-CRP in serum in simple ACI group ? ACI inducing SIRS group and ACI inducing SIRS to MODS group were higher than those in normal control group,the difference was statistically significant(P < 0.05).Compared with the simple ACI group,ACI inducing SIRS and ACI inducing SIRS to MODS are higher(P < 0.05),the difference between ACI inducing SIRS group and ACI inducing SIRS to MODS group was also statistically significant(P < 0.05).6.The data of endotoxin in the normal control group,simple ACI group,ACI inducing SIRS group,ACI inducing SIRS to MODS group in peripheral blood were: 2.23±1.75EU/ml?4.65±2.37 EU/ml?11.97±3.69 EU/ml?14.47±4.50 EU/ml.The levels of endotoxin in serum in simple ACI group ?ACI inducing SIRS group and ACI inducing SIRS to MODS group were higher than those in normal control group,the difference was statistically significant(P < 0.05).Compared with the simpleACI group,ACI inducing SIRS and ACI inducing SIRS to MODS are higher(P< 0.05),the difference between ACI inducing SIRS group and ACI inducing SIRS to MODS group was also statistically significant(P < 0.05).Conclusion:1.ACI can induce SIRS and even lead to MODS.2.Proinflammatory cytokines were increased in simple ACI group ? ACI inducing SIRS group and ACI inducing SIRS to MODS group,whereas anti-inflammatory cytokines were reduced,there was an imbalance between pro-inflammatory cytokines and anti-inflammatory cytokines in these patients.3.The changes of Th17 cells and Treg cells in the peripheral blood of the simple ACI patients were in the opposite direction,and there was the imbalance of Th17/Treg cells.The Th17/Treg cell imbalance in ACI inducing SIRS group and ACI inducing SIRS to MODS group were more obvious.Th17/Treg cells may be involved in the development of SIRS and MODS after acute cerebral infarction and acute cerebral infarction,and Th17 cells may play a role in promoting,Treg cells may play an inhibitory role.4.The levels of hs-CRP and endotoxin in ACI inducing SIRS and ACI inducing SIRS to MODS group were significantly higher than those in the simple ACI group,suggesting that hs-CRP and endotoxin can be used as indicators to judge the condition of ACI in clinical work.