The Roles Of Different Lymphocyte Subsets In Acute Experimental Pancreatitis

Despite improvements in intensive care treatment during the past few decades, thedeath rate for AP has not declined signifcantly. Most studies believe that manyinflammatory factor contribute to serious circulatory, respiratory, urinary and nervoussystem damage in SAP. However the majority of patients with acute pancreatitis canprevent excessive inflammatory response development, so that pancreatitis is mild withself-healing tendency. Why would about twenty percent of patients will develop SAP.There are several hypotheses attempting to explain this phenomenon, but its mechanismstill has not been clarified. At present a growing number of scholars have argued disturbedbalance between pro-inflammatory and anti-inflammatory cytokines play a important role.Lymphocytes play a multifunctional role in the immune system, to be used to mediatehumoral immunity and cellular immunity. Particularly, lymphocytes in peripheral bloodmononuclear cells (PBMC) are key potent regulators immune function, so that once thedanger of infection has passed, the system can return to relative calm and further damagecan be avoided. Then, further study of lymphocytes in acute pancreatitis immune function is the key to a better understanding of the occurrence and development of SAP.To date, no defnitive treatment options for SAP are available. Treatment is limited togeneral supportive care. Therefore, novel therapeutic strategies are needed urgently toreduce mortality and morbidity associated with AP. MSCs is their potentimmunosuppressive activities that have attracted much attention in novel therapeuticstrategies for immunomodulation. Currently, no defnite therapeutic options for SAP exist.The potential of UCMSCs to cure AP make them an attractive potential therapeutic tool inthe future.【Objectives】1.To Study on function of Tand B-lymphocytes in acute pancreatitis;2To compare ofBregs in acute pancreatitis;3.To investigate the role of umbilical cord mesenchymal stemcells (UCMSCs) in treating sever acute pancreatitis (SAP) of rats.【Materials and methods】1.Acute pancreatitis was induced by intraperitoneal injections of cerulein in Tcell-deficient and wild-type mice; B cell-deficientand wild-type mice; T and B celldeficient group and wild-type mice;2.The severity of acute pancreatitis was assessed byserum levels of amylase,wet/dry ratio of pancreas and pancreatic/pulmonary histology;3.Expression of infammation mediators and cytokines were evaluated by Enzyme-LinkedImmunosorbnent Assay4.The characterization of Bregs in SAP were determined by flowcytometry analysis (FACS);5.To analysis the relationship between alteration of Bregscontent and inflammation during acute pancreatitis model;6.We use the taurocholateinduced model of acute sever pancreatitis in rats;7.infused UCMSCs administration torats at four different time points (immediately,1hour,6hours,12hours after the inductionof SAP) through the tail vein and at different dose (20ml/kg，10ml/kg，1ml/kg，0.1ml/kg)at1hours after the induction of SAP;7. The severity of acute pancreatitis was assessed bythe mortality rate, ascites, and serum amylase were recorded, pancreatic and pulmonarytissues were harvested for histopathological study and edema evaluation.【Results】1．T cells and B cells have different roles in acute experimental pancreatitis In both T cell-deficient group and T and B cell-deficient group, serum amylase,pancreatic edema and histological lesion were significantly decreased and the productionof TNF-α and IFN-γ were reduced, whereas those were significantly increased in BCell-deficient group during cerulein-induced AP. Furthermore, As compared to wild-type,Both T cell-deficient mice and T and B cell-deficient mice significantly ameliorated lunginjury. An opposite pattern was observed in B cell-deficient mice and wild-type mice withsevere injury, but the difference was not statistically significant（P＞0.05）2．Changes of Bregs in severe acute pancreatitisPatients with sever acute pancreatitis show impaired early activation of Bregs; Theseverity of acute pancreatitis were correlated negatively with Bregs, positively withinfammation in mice withAP.3． Effects of UCMSCs in a rat model of acute pancreatitisInfused UCMSCs reduced the mortality rate from58%to17%and caused asignificant decrease of serum amylase, expression of infammation mediators andcytokines pancreatic and pulmonary morphological alterations. The earlier and more dosetreatment was better effective.【Conclusions】This study confirmed the participation of lymphocytes are important inflammatorydisorders in acute pancreatitis. T cell play a main roles to promote inflammation responseand B cell inhibitor inflammatory response in acute pancreatitis, the mechanism may bethat Bregs, a subtype of B lymphocytes, inhibits excessive inflammatory response. Usingumbilical cord-derived mesenchymal stem cells may significantly reduce injury andtreatment effect of SAP with a time-dependent and dose-dependent manner.