FibertypespecificexpressionofTNF-alpha,IL-6andIL-18inhumanskeletalmusclesRunningtitle:CytokineExpressionisFiberTypeDependentPeterPlomgaard1,MilenaPenkowa2,BenteK.Pedersen1(1)CentreofInflammationandMetabolismatTheDepartmentofInfectiousDiseasesandTheCopenhagenMuscleResearchCentre,Rigshospitalet,(2)CentreofInflammationandMetabolism&SectionofNeuroprotectionatThePanumInstituteAllaffiliationsarewithinTheFacultyofHealthSciences,UniversityofCopenhagen,DenmarkAbstractSkeletalmuscleisnowrecognizedasanendocrineorganwiththecapacitytopro-ducesignalpeptidesinresponsetomusclecontractions.Herewedemonstratethatrestinghealthyhumanmusclesexpresscytokinesinafibertypespecificman-ner.Humanmusclebiopsiesfromsevenhealthyyoungmaleswereobtainedfromm.triceps,m.quadricepsvastuslateralisandm.soleus.TypeIfiberscontributed(mean±SE)24.0±2.5%intricepsoftotalfibers,51.3±2.4%invastusand84.9±2.2%insoleus.Asexpected,differencesinthefibertypecompositionwereaccompaniedbymarkeddifferencesbetweenthethreemuscleswithregardtoMHCIandMHCIIamRNAexpression.Immunohistochemistrydemonstratedthattumornecrosisfactor(TNF)-αandinterleukin(IL)-18weresolelyexpressedbytypeIIfibers,whereastheexpres-sionofIL-6wasmoreprominentintypeIcomparedtotypeIIfibers.Thefibertypespecificitywasfoundintriceps,vastusandsoleusindicatingthatthelevelofdailymuscleactivitydidnotinfluencebasalcytokineexpression.Thespecificityofcytokineexpressionindifferentmusclefibertypesinhealthyyoungmalessuggeststhatcytokinesmayplayspecificregulatoryrolesinnormalphysiology.Keywords:soleus;triceps;vastus;musclebiopsy;inflammationIntroductionAgrowingbodyofliterature(33)indicatesthatcytokinesareinvolvedinthereg-ulationofskeletalmusclefunction.Amongcytokines,tumornecrosisfactor-α(TNF-α)isthecytokinemostprominentlylinkedtomusclepathophysiology.TNF-αhasbeenassociatedwithmusclecatabolismandlossofmusclefunctionCytokineExpressionisFiberTypeDependent•53Addresscorrespondenceto:PeterPlomgaard,CentreofInflammationandMetabolism,Rigshospitalet,Section7641,Blegdams...
