Expression Of IL-33 In Early Peripheral Blood And Regulation Of Th1/Th2 Balance In Patients With Sepsis

Research backgroundSepsis has always been a major problem in the department of critical care medicine.It not only brings great burden to the family of patients,but also hinders the progress and development of medical and health services which is a serious disease with a high cost of treatment and a high mortality rate.But because of the pathologic mechanism of sepsis itself is complex,the medical community have been unable to agree on which is right.Therefore,it is urgent to find out the pathological mechanism of the development of sepsis,and to provide new ideas and directions for the targeted treatment of the disease.Referring to many related literature and data,we know that the pathogenesis of sepsis mainly involves immune suppression or immune paralysis,abnormal coagulation function,imbalance of inflammatory response(SIRS and CARS coexist),gene polymorphism and so on.In particular,the imbalance of immune inflammation has been a hot spot of research in recent years.IL-33 who has long been called the warning element in the early stage of inflammation was discovered in 2005 as a new member of the IL-1 family.IL-33 has always been popular especially in the IL-33/ST2 signaling pathways.But how it participates in the development of sepsis,the answer is still unclear.The research of IL-33 in sepsis is less and less.And as an important immune cell in the body,the T cell subgroup(Th1/Th2)is also involved in the development of sepsis.The aim of this study is to study the changes of IL-33 in peripheral blood of patients with sepsis,and to find out the rules to provide a probable evidence for the effective immunotherapy of sepsis;At the same time,we will explore the change of Th1/Th2 balance in sepsis patients by discussing the change of IFN-?/IL-4 ratio(IFN-? is secreted mainly by Th1 cells,and IL-4 is mainly secreted by Th2 cells).ObjectiveIn order to observe the change rule of interleukin 33(IL-33),soluble Suppression of Tumorigenicity 2(sST2),IFN-?,IL-4 and the ratio of IFN-?/IL-4 in the peripheral blood plasma of patients with sepsis at the early stage.The changes in the IFN-?/IL-4 ratio in the patients with sepsis will be observed to analyze the Th1/Th2 cell drift and meanwhile find the correlation between it and IL-33.At the same time,discuss the evaluation and prognostic value of IL-33 for infectious diseases in patients with sepsis.MethodsA total of 40 patients with sepsis who were admitted to ICU in Liaocheng People's Hospital from December 2016 to December 2017 by a single center,prospective,single blind and control research method were selected as the case group.According to the 28 day prognosis,the sepsis group(Also called the case group)was divided into the survival group and the death group.At the corresponding period,20 healthy volunteers in health examination center which belongs to the Liaocheng People's Hospital were selected as the healthy control group.Analyze the level of IL-33,sST2,IFN-?,IL-4 with the method of enzyme linked immunosorbent assay(ELISA),and simultaneously analyze the level of procalcitonin(PCT)with enzyme-linked fluorescent immuno-assay(ELFA)within 3hours and 3days after entering ICU.The acute physiology and chronic health evaluation system II(APACHE II)score of sepsis patients was calculated.Meanwhile,ICU hospitalization time,mechanical ventilation time and prognosis after 28 d were recorded.Compare the changes of above indicators between healthy control group and sepsis group within 3 hours,two subgroups of sepsis at different times(Group 3 hours and 3 days),the survival group and the death group.Analyze the correlation between IL-33 and APACHE II score,sST2,IFN-?,IL-4 and PCT in septic patients with Spearman.Result1.The levels of IL-33,sST2,IFN-? and IL-4 in sepsis group within 3 hours were significantly higher than those in the healthy control group,and the difference was statistically significant(P<0.05).2.As time goes on,the levels of IL-33,sST2,IFN-?,APACHE II score and PCT in sepsis group within 3 days were obviously lower than those in sepsis group within 3 hours and the difference was statistically significant(P<0.05).While the level of IL-4 decreased,but there was no statistical significance(P>0.05).3.The healthy control group,survival group and death group were compared among the three groups: The ratio of IFN-?/IL-4 in the latter two groups was lower than that in the healthy control group(P<0.05);There was no significant difference in the ratio of IFN-?/IL-4 between survival group and death group within 3 hours(P>0.05);As time prolonged,the ratio of IFN-?/IL-4 in the death group decreased more significantly than that in the survival group(P<0.05).As far as the survival group was concerned,the ratio of IFN-?/IL-4 was not significantly changed with the duration of hospitalization(P > 0.05).However,the ratio was significantly decreased with the duration of hospitalization in the death group(P<0.05).4.In patients with sepsis group,IL-33 was positively correlated with PCT,sST2 and IFN-? when they entered ICU 3 hours(P<0.05).After 3 days,IL-33 was positively correlated with the score of APACHE II,PCT,IFN-? and IL-4(P<0.05).Conclusion1.The levels of IL-33 in septic group began to rise when they entered ICU.2.The decrease of IFN-?/IL-4 ratio at the early stage of sepsis suggested that the helper T cell had been polarized,which meant that the balance of Th1/Th2 was drifting to Th2,that was,the presence of immunosuppression.Especially in the death group,this immunosuppressive phenomenon was more significant,which suggested poor prognosis.3.IL-33 has a high value in the evaluation of the condition of sepsis and the evaluation of the prognosis.SignificanceThis trial had opened our eyes to the changes of IL-33 and related immune indexes,moreover broadened our horizon in the drift and immune state of T cell subsets(Th1/Th2)through the change of IFN-? /IL-4 ratio in early stage of sepsis,which will provide a possible new way of thinking for the immunotherapy of sepsis.