Therapeutic efficacy of CXCR3 blockade in an experimental model of severe sepsis 英文参考文献.docVIP

Herzigetal.CriticalCare2012,16:R168 /content/16/5/R168 RESEARCH OpenAccess TherapeuticefficacyofCXCR3blockadeinan experimentalmodelofseveresepsis DanielaSHerzig1,YinGuo1,2,GepingFang1,TracyEToliver-Kinsky1,3 andEdwardRSherwood4* Abstract Introduction:InourpreviousstudieswedemonstratedthatCXCchemokinereceptor3(CXCR3)participatesinthe regulationoflymphocytetraffickingduringcecalligationandpuncture(CLP)-inducedsepsis.Inthisstudy,we evaluatedtheeffectsoftreatmentwithanti-CXCR3immunoglobulin(IgG)andantibioticsonoutcomeduring septicshockcausedbyCLP. Methods:C57BL/6JmiceweretreatedwithneutralizingIgGagainstCXCR3plusPrimaxineither24hourspriorto, 2hoursafteror6hoursafterCLP.ControlmicereceivednonspecificIgGplusPrimaxininthesameregimen. Survival,corebodytemperature,bacterialclearanceandsystemiccytokineproductionwereevaluated. Results:Ourresultsshowthattreatmentwithanti-CXCR3IgGplusPrimaxinsignificantlyimprovedsurvivalwhen administered24hourspriortoCLP(50%vs.10%),2hoursafterCLP(55%vs.10%)or6hoursafterCLP(55%vs. 25%)comparedwithmicereceivingnonspecificIgGplusPrimaxin.Treatmentwithanti-CXCR3plusPrimaxin24 hourspriortoCLPattenuatedhypothermiaandIL-6andmacrophageinflammatoryprotein2(MIP-2)production butdidnotalterbacterialclearance.Treatmentwithanti-CXCR3IgGandPrimaxin2hoursafterCLPdidnot improvebacterialclearanceandsystemiccytokineproductioncomparedwithmicetreatedwithIgGandPrimaxin, whereas6hoursafterCLPthebacterialclearanceandIL-6andMIP-2concentrations,bothinplasmaand peritoneallavagefluid,weresignificantlyimprovedinmicereceivinganti-CXCR3IgGandPrimaxincomparedwith micethatonlyreceivednonspecificIgGandPrimaxin. Conclusion:TheresultsfromthisstudyindicatethatneutralizationofCXCR3priorto,2hoursafteror6hoursafter theinitiationofCLP-inducedsepticshockimprovessurvivalandattenuatesCLP-inducedinflammationand physiologicdysfunction. Introduction additivelytoregulatelymphocytetrafficking, depending CXC chemokine receptor 3 (CXCR3) is a G-protein onthediseaseprocessandtissueunderst