Urinechemokinelevelscorrelatewithtreatmentresponsetophosphodiesterase4inhibitorinprostatitis

摘要： AIMToinvestigatetheassociationofurinarychemokineswiththetreatmentresponseinchronicprostatitis/chronicpelvicpainsyndrome(CP/CPPS)patients.METHODSBetween2007-2011,18outof21maleCP/CPPSpatientsmettheexclusion/inclusioncriteriaofthe16wklongitudinalstudyontwicedailyoraltreatmentwithPhosphodiesterase4inhibitorcalledApremilastfor12wk.Symptomscoresandurinespecimenwerecollectedatbaselineandeveryvisitat4wkintervalfromCP/CPPSpatientswhocompletedatleast8wkofdrugtreatment.UrinecollectedateachvisitwasfrozenandthenanalyzedtogetherafterthawingforchemokinesandgrowthfactorsusingMILLIPLEX?MAPimmunoassay.CrosssectionalassociationofChronicProstatitisSymptomIndex(CPSI)andvisualanalogscale(VAS)withchemokinelevelsinurinecollectedatbaselinewasassessedin18CP/CPPSpatientsrelativeto10asymptomaticmalesubjects.Longitudinalassociationbetweenurinechemokinelevelsandsymptomscoreswasassessedin8treatmentadherentCP/CPPSpatientsatbaselineandat4,8,12and16wk.RESULTSUrinechemokineslevelsofCXCL-1(GRO-a),CXCL-8(IL-8),CXCL-10(IP-10)andCCL5(RANTES)inCP/CPPSpatientsatbaselineweresignificantlyelevatedrelativetoasymptomaticsubjects,whereaslevelsofsIL-1RAinCP/CPPSweresignificantlylowercomparedtocontrols(P<0.05).Quantitatively,urinelevelsofCXCL-10werehigherthanotherchemokinesinCP/CPPS,butitsfoldchangeof5relativetocontrolswaslowerthanthe20foldchangenotedforCXCL-8.Themeanageofenrolledpatientswhocompletedatleast8wkoftreatment(n=8)was46.5±9.4yearsandanalysisfoundthatelevationofCXCL-8andCCL5increasedtheoddsforhigherscoreofCPSIby54%and25%,respectively(Ftest,P=0.00007).UrinelevelsofCCL2(MCP-1)andCXCL-10togetherexplainedapproximately85%ofvarianceinlongitudinaldataonmultivariateanalysis.Bivariateanalysisof5patientswhofullycompliedandcompletedtheassigneddoseregimen,showedstronglinearcorrelationofreducedurinelevelsofCXCL-10,CXCL-8,CCL5,CCL2andPDGFwithimprovementinclinicalactivityasmeasuredbypainVASandCPSI(Pearsonr=0.83-0.97;P<0.05).CONCLUSIONUrinelevelsofCXCL-10,CCL2andPDGFcanbesensitive,objectiveandnon-invasivemarkersofresponsetonewtherapeuticinterventioninCP/CPPSpatients. ... （共9页）