Changes On Levels Of Sphingosine Kinase1in Patients With Acute Pancreatitis

Background：As an inflammatory process, acute pancreatitis(AP) results in anexcessive leukocyte activation and increased migration of neutrophils to theinflamed area with a consequent release of proinflammatory mediatorsincluding interleukins (IL-1b,IL-6, IL-8, IL-10, IL-18) and Tumor NecrosisFactor-alpha (TNF-α). These mediators have been involved with thepathogenesis of progression of a pancreatic infection to necrosis andconsequently to SIRS and multiorgan failure. Although a great deal is knownregarding etiology of AP, the molecular and pathophysiological mechanismsunderlying it remain unclear.Sphingosine kinase1(SphK1) is an intracellularsignaling enzyme that catalyzes the phosphorylation of sphingosine tosphingosine-1-phosphate (S1P) which has been implicated in many biologicalprocesses. SphK1and its product S1P have been implicated in inflammatoryresponse and various immune cell functions. However,the changes of SphK1inAP and the potential role for it in inflammatory response in AP are still unclear.Objective:To detect the levels of Sphingosine Kinase1(SphK1) of peripheralblood leucocyte in the patients with AP,investigating the role of SphK1ininflammatory response in AP.Method:Thirty patients with AP wereenrolled.Criteria for the clinical diagnosis of AP：1.Attack of acute abdominalpain and tenderness in the upper abdomen;2.Increased levels of pancreatic enzymes in blood or urine，≥3times the upper limits of normal;3.Abnormalimaging findings in pancreas associated with AP；Patients having two or moreof the above three criteria are diagnosed with acute pancreatitis.All patientswith AP were divided into severe acute pancreatitis(SAP) group（n=13） andmild acute pancreatitis(MAP) group(n=17) according to Atlanta classificationof acute pancreatitis(1992).10health volunteers were selected as health controlsubjects. Acute Physiological and Chronic Health(APACHE)II score wereevaluated at48h,72h,5d,7d after the attack of AP. The serum levels of TNF-α，IL-6, the levels of SphK1mRNA and enzymatic activity of peripheral bloodleucocyte in patients with AP were measured at48h,72h,5d,7d after the attackof AP. The serum levels of TNF-α，IL-6, the levels of SphK1mRNA andenzymatic activity of peripheral blood leucocyte in health control subjects weremeasured at48h,72h,5d,7d after being included. Resrults:1.At48h,72h,5d and7d, the levels of SphK1mRNA of peripheral blood leucocyte with AP wereelevated compared with htalthy controls（P <0.05），also the levels of SphK1enzymatic activity of peripheral blood leucocyte with AP were elevatedcompared with htalthy controls（P <0.05）.2.At48h,72h and5d, compared thelevels of SphK1mRNA and enzymatic activity of peripheral blood leucocyteamong htalthy controls,MAP and SAP: htalthy controls<MAP<SAP（P <0.05）; At48h,72h and5d, compared the concentration of serum TNF-α，IL-6among htalthy controls,MAP and SAP: htalthy controls<MAP<SAP（P <0.05）.The levels of serum TNF-α，IL-6showed similar shift with intracellular SphK1expression.3.At48h,72h,5d and7d,SphK1mRNA expression werepositively correlative with APACHEII score of AP patients.4.Using ROCanalyses SphK1.The highest sensitivity and diagnostic accuracy for SphK1wasobserved at48h,and the area under ROC curve was0.946.This suggests SphK1is of great value in early diagnosis of SAP.Conclusion:1. The levels of serumTNF-α，IL-6showed similar shift with intracellular SphK1expression inpatients with AP.Activated SphK1may be implicated in inflammatory responsein AP.2. SphK1is of great value in early diagnosis of SAP.The expression ofSphK1were positively correlative with APACHEII score of APpatients.Measurement of SphK1of peripheral blood leucocyte is an accurateand method in the early prognosis of AP.