Role of interleukin‐18 in intrahepatic inflammatory cell recruitment in acute liver injury

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: neutrophil;    macrophage;    NKT cell;    chemokine;    IL‐;    18;   

DOI  :  10.1189/jlb.0710412

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Althoughtheinnateimmunesystemhasbeendemonstratedtoplayimportantrolesasthefirstlineofdefenseagainstvariousinfections,littleisknownabouttheinteractionsbetweenintrahepaticinflammatorycellsandthecytokinenetworkintheliver.Here,weexaminedtheroleofIL‐18inIHLrecruitmentinacuteliverinjury.C57BL/6micewereinjectedwithanαCD40mAb,andtheirserumIL‐18levelswereobservedtoincrease,withsubsequentrecruitmentofIHLsintotheliver.NKTcellswereinvolvedinthisliverinjury,astheserumALTlevelswerereducedinNKTKOmicethroughthesuppressionofmacrophageandmonocytemigrationandcytokineproduction.Incontrast,depletionofneutrophilsexacerbatedtheliverinjuryassociatedwithhighlevelsofTNF‐αandIL‐18andincreasednumbersofmacrophagesandmonocytes.TreatmentwithaneutralizingantibodyagainstIL‐18reducedtheserumALTlevelsandinflammatorycellaccumulationintheliver.Finally,additionaladministrationofrIL‐18withαCD40injectioncausedsevereliverinjurywithincreasedIFN‐γproductionbyNKcells.Inconclusion,thesefindingsdemonstratethatIL‐18modulatesliverinflammationbytherecruitmentofinflammatorycells,includingNKTcells,macrophages,monocytes,andneutrophils...

【 授权许可】

CC BY