Regulation Of The M2Anti-inflammatory Kupffer Cells By IL-4and CD4~+CD25~+FoxP3~+Regulatory T Cells On Severe Acute Pancreatitis In Mice

Objective:To investigate the effective method of inducing severe acute pancreatitis with cerulein pluslipopolysaccharide (LPS) and the regulation of the M2anti-inflammatory kupffer cells by IL-4andCD4+CD25+FoxP3+regulatoryTcellsonsevereacutepancreatitisinmice.Methods:Normal group was induced by intraperitoneal injection of saline；model group was induced byintraperitonealinjectionofceruleinplusLPS.Modelgroupwasdividedintothreegroups：9h、12hand24hgroups after induction of SAP. Histopathological alterations of pancreatic tissues were evaluated amongthese three groups.2. Expressions of inflammatory cytokines mRNA in liver tissues were assessed byreal-timefluorescentquantitativereversetranscriptasepolymerasechainreaction(RT-PCR)betweennormalgroup and SAP8h+NS group. The mice of SAPmodels were divided into three groups in accordance withtheintravenousinjectionofthedifferentsolutions：SAPwithsalineinjectiongroup、SAPwithIL-4injectiongroup and SAPwith Treg injection group. Expression of IL-1β、TNF-α and IL-10mRNAin liver tissueswere assessed by RT-PCR；Expressions of CD163and CCR7in liver were assessed by confocalimmunofluorescencemicroscopy.Results:(1)TheresultsofHEstaining：pancreaticedema、inflammationandacinarcellnecrosisin24hgroupsafterinductionofSAP.(2)TheexpressionsofIL-1βandTNF-αmRNAinlivertissuesofSAP8h+NSgroupweresignificantlyhigherthanthoseofnormalgroup（P<0.1）.(3)TheexpressionsofIL-1βmRNAinlivertissuesofSAP16h+TreggroupandSAP16h+IL-4groupweresignificantlylowerthanthoseofSAP16h+NSgroup（P<0.1)）；TheexpressionofIL-1βmRNAinlivertissuesofSAP16h+TreggroupwassignificantlylowerthanthoseofSAP16h+IL-4group（P<0.05）；TheexpressionsofTNF-αmRNAinlivertissuesofSAP16h+TreggroupandSAP16h+IL-4group weresignificantlylowerthanthoseofSAP16h+NSgroup（（P<0.1）；TheexpressionofTNF-αmRNAinlivertissuesofSAP16h+TreggroupwassignificantlylowerthanthoseofSAP16h+IL-4group（P<0.1）；TheexpressionofIL-10mRNAinlivertissuesofSAP16h+IL-4group wassignificantlyhigherthanthoseofSAP16h+NSgroupand SAP16h+Treggroup（P<0.1）.Conclusion:It is a effective method using cerulein plus LPS to induce severe acute pancreatitis in mice. Kuffer cells arevery important in the development of SAP. IL-4and Treg promote the expression of the M2anti-inflammatorykupffercells，andthedown-regulationofTNF-α、IL-1βandCCR7andup-regulationofIL-10andCD163suggestIL-4andTreghavetherapeuticeffectsonSAP.