Intravenous immunoglobulin skews macrophages to an anti‐inflammatory, IL‐10‐producing activation state

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

关键词: macrophage activation;    regulatory macrophages;    Fc receptors;    map kinases;    sepsis;   

DOI  :  10.1189/jlb.3VMA0315-078R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

IntravenousIgisusedtotreatautoimmuneorautoinflammatorydisorders,butthemechanismbywhichitexertsitsimmunosuppressiveactivityisnotunderstoodcompletely.ToexaminetheimpactofintravenousIgonmacrophages,wecomparedcytokineproductionbyLPS‐activatedmacrophagesinthepresenceandabsenceofintravenousIg.IntravenousIgtreatmentinducedrobustproductionofIL‐10inresponsetoLPS,relativetoLPSstimulationalone,andreducedproductionofproinflammatorycytokines.Thisanti‐inflammatory,intravenousIg‐inducedactivationwassustainedfor24hbutcouldonlybeinducedifintravenousIgwereprovidedwithin1hofLPSstimulation.IntravenousIgactivationledtoenhancedandprolongedactivationofMAPKs,Erk1/2,p38,andErk5,andinhibitionofeachreducedintravenousIg‐inducedIL‐10productionandsuppressionofIL‐12/23p40.IL‐10productionoccurredrapidlyinresponsetointravenousIg+LPSandwassufficienttoreduceproinflammatoryIL‐12/23p40productioninresponsetoLPS.IL‐10inductionandreducedIL‐12/23p40productionweretranscriptionallyregulated.IL‐10playedadirectroleinreducingproinflammatorycytokineproductionbymacrophagestreatedwithintravenousIg+LPS,asmacrophagesfrommicedeficientintheIL‐10RβchainorinIL‐10werecompromisedintheirabilitytoreduceproinflammatorycytokineproduction.Finally,intraperitonealinjectionofintravenousIgorintravenousIg+LPSintomiceactivatedmacrophagestoproducehighlevelsofIL‐10duringsubsequentorconcurrentLPSchallenge,respectively.ThesefindingsidentifyIL‐10asakeyanti‐inflammatorymediatorproducedbyintravenousIg‐treatedmacrophagesandprovideinsightintoanovelmechanismbywhichintravenousIgmaydampendowninflammatoryresponsesinpatientswithautoimmuneorautoinflammatorydiseases...

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