Seite - 18 - in Advances in Neuroimmunology

brain sciences Article Astrocytic IL-6Influences theClinicalSymptomsof EAEinMice MariaErta 1,2,MercedesGiralt 1,2,SilviaJiménez1,AmaliaMolinero1,2,GemmaComes1,2 and JuanHidalgo1,2,* 1 DepartmentofCellularBiology,PhysiologyandImmunology,AnimalPhysiologyUnit, FacultyofBiosciences,UniversitatAutònomadeBarcelona,Bellaterra08193,Spain; mariaerta@gmail.com(M.E.);merce.giralt@uab.es (M.G.); siljiba@gmail.com(S.J.); amalia.molinero@uab.es (A.M.);gemma.comes@uab.es (G.C.) 2 InstituteofNeurosciences,UniversitatAutònomadeBarcelona,Bellaterra08193,Spain * Correspondence: Juan.Hidalgo@uab.es;Tel.:+34-935-812-037;Fax:+34-935-812-390 AcademicEditor:DonnaGruol Received: 12February2016;Accepted: 10May2016;Published: 17May2016 Abstract: Interleukin-6 (IL-6) is amultifunctional cytokine that not onlyplaysmajor roles in the immunesystem,butalsoservesasacoordinatorbetweenthenervousandendocrinesystems. IL-6 is produced inmultiple cell types in theCNS, and in turn,many cells respond to it. It is therefore important toascertainwhichcell type is thekeyresponder to IL-6duringbothphysiological and pathological conditions. Inorder to test theroleofastrocytic IL-6 inneuroinflammation,westudied anextensively-usedanimalmodelofmultiplesclerosis, experimentalautoimmuneencephalomyelitis (EAE), inmicewith an IL-6 deficiency in astrocytes (Ast-IL-6KO). Results indicate that lack of astrocytic IL-6didnotcausemajorchanges inEAEsymptomatology.However,adelay intheonsetof clinical signswasobservedinAst-IL-6KOfemales,withfewer inflammatory infiltratesanddecreased demyelinationandsomealterations ingliosisandvasogenesis, comparedtofloxedmice. Theseresults suggest thatastrocyte-secretedIL-6hassomeroles inEAEpathogenesis,at least infemales. Keywords: interleukin-6;astrocyte;EAE 1. Introduction Interleukin6(IL-6) isamultifunctional four-helixbundlecytokine,originally identifiedasaB-cell differentiationfactor in1985[1],whichhasbeenlinkedtonumerousbiological functions. It isnowknown tobeoneof themaincytokinescontrollingtheimmunesystem,andinaddition, itactsasacoordinator betweenthenervousandendocrinesystems. IL-6playsanessential role inthecentralnervoussystem (CNS) inmanyphysiological, inflammatoryanddiseaseconditions,beingable toexertdualactions(fora review,see[2]).Althoughmanycells intheCNSproduceIL-6[3],astrocytesarethemainproducer[2,4]. Multiple sclerosis (MS) is oneof themost common inflammatorydisorders of theCNSanda leadingcauseofdisability inyoungadults. It isestimatedthat2–2.5millionpeoplearecurrently living withthisdemyelinatingdiseaseworldwide[5]. Itspathologicalhallmarksconsistof localdemyelination, inflammationandvariableaxonaldestruction. Experimentalautoimmuneencephalomyelitis (EAE) [6] is awell-knownanimalmodel to study this inflammatory condition. Cytokines arekeymediators in thepathogenesisof inflammatory lesions inCNS,presentingbothhelpfulandharmfuleffects [7]. IL-6playsacrucial role inMSasdemonstratedbyitspresence inacuteandchronicactiveplaquesof MSpatients [8]. Inaddition, it hasbeenshownthat IL-6-deficientmiceare resistant toEAE[9–13] presumably because of a lack of differentiation of naive T cells intoMOG-specific T helper cells producingIL-17 (Th17)andthesubsequentreductionof their infiltration into theCNS[14], although theexactmechanismisnot fullyunderstood. BrainSci. 2016,6, 15 18 www.mdpi.com/journal/brainsci