IL-6isapleiotropiccytokinewithawiderangeofBIOLOGicalactivitiesinimmuneregulation,hematopoiesis,inflammation,andoncogenesis.IL-6signalsthroughacell-surfacetypeIcytokinereceptorcomplexconsistingoftheligand-bindingIL-6Rαchain(CD126),andthesignaltransducingcomponentgp130(CD130).Signaltransductionthroughgp130,thecommonsignaltransducerofcytokinesrelatedtoIL-6,ismediatedbytheJAK–STATpathwayandtheRAS–MAPKpathway.Inadditiontothemembrane-boundreceptor,asolubleformofIL-6R(sIL-6R)hasbeenpurifiedfromhumanserumandurine.ThesIL-6R/IL-6complexcanstimulateneuriteoutgrowthandpromotesurvivalofneurons,andhencemaybeimportantinnerveregenerationthroughremyelination.IL-6isrelevanttomanydiseaseprocessessuchasdiabetes,atherosclerosis,depression,Alzheimer’sdisease,systemiclupuserythematosus,prostatecancer,andrheumatoidarthritis.Thereisaninterestindevelopinganti-IL-6agentsastherapyagainstmanyofthesediseases.Examplesofsuchtherapeuticagentsincludetocilizumab,whichhasbeenapprovedforrheumatoidarthritisandALD518,describedinclinicaltrials(2-5).HumanIL-6isactiveonmouseandratcells.RecombinantHumanIL-6ACFisanon-glycosylatedproteincontaining184aminoacids,withamolecularweightof21kDa.
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