Modulation of granulocyte kinetics by GM‐CSF/IFN‐γ in a human LPS rechallenge model

[摘要] InflammationinresponsetoinfectionortraumacanleadtoCARS,whichischaracterizedbyleukocytedysfunction.Inthisstudy,weusedahumanmodelsystemforCARStostudytheeffectofGM‐CSFandIFN‐γtreatmentonthisimmunoparalyzedstate.HealthyhumanvolunteersweretreatedwithGM‐CSF(4μg/kg),IFN‐γ(100μg),orplaceboinbetweentwochallengeswithEscherichiacoliLPS/endotoxin(2ng/kg).Serialleukocytebloodcountsweremeasured.NeutrophilsubsetswerediscriminatedusingCD16andCD62Lexpression.LPSrechallengeresultedinincreasedmobilizationofmatureneutrophils,whereasbandedneutrophilsdecreased.GM‐CSFandIFN‐γtreatmentdidnotrestorethesechanges.GM‐CSFtreatmentdid,however,increasethenumberofCD16bright/CD62LdimneutrophilsthatwerepreviouslyshownbeabletosuppressTcellproliferation.IFN‐γtreatmentdecreasedneutrophiliaseenafterLPSrechallenge.OurstudyshowsthatLPSrechallengewasassociatedwithchangesinthedistributionofneutrophilsubsets,whereasnoadditionalchangesinkineticsofothergranulocytepopulationswereobserved.GM‐CSFandIFN‐γtreatmentinducedashiftingranulocytecompositiontowardananti‐inflammatorydirectionbyincreasingCD16bright/CD62Ldimcellsordecreasingneutrophilcounts,respectively...

[学科分类] 生理学

[关键词] neutrophil;eosinophil;myeloid‐derived suppressor cells;endotoxemia;endotoxin tolerance