Inflammationisaphysiologicalresponseoftheimmunesystemtoinjuryandinfection.Thisprocesssignalstheimmunesystemtohealandrepairdamagedtissue,aswellastodefenditselfagainstinfectiveagents,suchasvirusesandbacteria.However,unresolvedorinappropriatelyactivatedinflammationcanbecomepathogenic1.Chronicinflammationistheprimarycauseofabroadspectrumofdiseases,includingrheumatoidarthritis(RA),inflammatoryboweldisease(IBD;includinggastrointestinalconditionssuchasCrohn’sdiseaseandulcerativecolitis),chronicobstructivepulmonarydisease(COPD),asthma,psoriasisandidiopathicpulmonaryfibrosis(IPF),amongothers1.Viralandbacterialinfectionsorotherinsults(suchtoxins,chemicalsandsoforth)canleadtouncontrolledacuteinflammatoryresponsesandinjuryoftenseeninpatientswithunderlyingpathogenicconditions(suchasCOPDorasthma).Acutelunginjury(ALI)isasyndromewithdiagnosticcriteriabasedonhypoxaemiaandaclassicalradiologicalappearance,withacuterespiratorydistresssyndrome(ARDS)atthesevereendofthediseasespectrumimpairinggasexchange,leadingtomultipleorganfailurewidespreadinflammationinthelungsandsepsis2.ArecentexampleofvirallyinducedALIandARDSincludesSARSCoV2infection,whichisassociatedwithacytokinestorm(characterizedbyhighlevelsofIL6,IL12andIL1β,andtumournecrosisfactor(TNF))anddefectivetypeIinterferonactivity3.Thisinflammatoryresponseresemblesthecytokinereleasesyndromeobservedinpatientsreceivingchimericantigenreceptor(CAR)TcelltherapyandbispecificTcellengagingantibodies,whichcanbetreatedwithanticytokinetherapytargetingtheIL6–IL6receptor(IL6R)signallingpathway3.Althoughselectbiologicsandkinaseinhibitors(seebelow)areeffectiveintreatingvariousinflammatorydiseases,alargeproportionofpatientsarenotresponsivetocurrenttherapies,andeffectivetreatmentapproachesforthissubsetofpatientsareneeded4.Autoimmunediseasesrefertoaspectrumofconditionsinwhichtheimmunesystemmistakenlyattacksone’sownbody5.Thisautoimmuneresponseofteninvolvesdysregulatedadaptiveimmunity(mediatedbyBandTlymphocytes)towardsa...
