Objective: To investigate the role of sphingosine kinase 1 (SphK1)/ sphingosine 1-phosphate (S1P) signaling in inflammatory response in severe acute pancreatitis (SAP). Background: SAP is an acute inflammatory process of the pancreas, which may lead to systemic inflammatory response syndrome and multiorgan dys- functionsyndrome.SphK1anditsproductS1Phavebeenimplicatedininflam- matory response and various immune cell functions. However, the potential role for SphK1/S1P in inflammatory response in SAP is still unclear. Methods: Twenty-two patients with SAP were enrolled in this study. SphK1 expression on peripheral neutrophils, monocytes, and lymphocytes was eval- uated by flow cytometry. SphK enzymatic activity in neutrophils and lym- phocytes was measured using a radiometric assay. The expression of S1P 1 and S1P 3 mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), and IL-6 were measured by ELISA. Results: TheexpressionofSphK1andSphKactivityweremarkedlyincreased in peripheral immune cells in the early stage of SAP and then reduced in the restoration stage in the patients. Moreover, we found that the level of S1P 3 mRNAinperipheralneutrophilsandlymphocytesofSAPpatientswassignifi- cantly elevated in the early stage as compared with the healthy volunteers, and it reduced in the restoration period. SphK1 expression on human peripheral neutrophils, monocytes, and CD4 + T lymphocytes were positively correlated with the APACHE (Acute Physiological and Chronic Health Evaluation) II scores in patients with SAP. The levels of serum proinflammatory cytokines including TNF-α, IL-1β, and IL-6 showed similar shifts with intracellular SphK1 expression in SAP patients. Conclusions: The authors identified a link between the SphK1 expression on peripheral immune cells and the severity of SAP. Observations showed a possible immunomodulating role for SphK1/S1P signaling in inflamma- tory response in SAP, suggesting that regulation of SphK1/S1P pathway may represent novel targets in the treatment of SAP.

第一署名医院：南京军区南京总医院