Statins accelerate the onset of collagen type II-induced arthritis in mice 英文参考文献.docVIP

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Statins accelerate the onset of collagen type II-induced arthritis in mice 英文参考文献.doc

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Vandebrieletal.ArthritisResearchTherapy2012,14:R90 /content/14/2/R90 RESEARCH ARTICLE OpenAccess Statinsacceleratetheonsetofcollagentype II-inducedarthritisinmice RobJVandebriel1*,HildaJIDeJong1,2,3,EricRGremmer1,OlafHKlungel3,Jan-WillemCohenTervaert4, WoutSlob5,JanWillemVanDerLaan6andHenkVanLoveren1,2 Abstract Introduction:Statins(hydroxymethylglutarylcoenzymeAreductaseinhibitors)areeffectiveinreducingtheriskof cardiovascularmorbidityandmortalityinpatientswithhyperlipidemia,hypertension,ortypeIIdiabetes.Nextto theircholesterol-loweringactivity,statinshaveimmunomodulatoryproperties.Basedontheseproperties,we hypothesizedthatstatinusemayeventuallyleadtodysregulationofimmuneresponses,possiblyresultingin autoimmunity.Wehaverecentlyshowninanobservationalstudythatstatinusewasassociatedwithanincreased riskofdevelopingrheumatoidarthritis.Ourobjectivewastoinvestigatewhetheracausalrelationshipcouldbe establishedforthisfinding. Methods:ThemousecollagentypeII(CII)-inducedarthritis(CIA)modelwasused,withimmunization,challenge, andeuthanasiaatdays0,21,and42,respectively.Statinsweregivenorallybefore(day-28untilday21)orafter (day21untilday42)CIAinduction.Atorvastatin(0.2mg/day)orpravastatin(0.8mg/day)wasadministered. Arthritiswasrecordedthreetimesaweek.Serumanti-CIIautoantibodiesandcytokinesinsupernatantsfrom Concanavalin-A-stimulatedlymphnodecellsandCII-stimulatedspleencellsweremeasured. Results:Statinadministrationacceleratedarthritisonsetandresultedin100%arthriticanimals,whereasonlyseven outof12nonstatincontrolanimalsdevelopedarthritis.AtorvastatinadministrationafterCIAinductionresultedin earlieronsetthanatorvastatinadministrationbeforeinduction,orthanpravastatinadministrationbeforeorafter induction.ThearthriticscoreofanimalsgivenpravastatinbeforeCIAinductionwassimilartothatofthenonstatin controls,whereastheothergroupsthatreceivedstatinsshowedhigherarthriticscores.Atorvastatinadministration, especiallybeforeCIAinduction,increasedanti-CIIautoantibodyproduction.IL-2andIL-17produ