TumorNecrosisFactor(TNF)wasoriginallydiscoveredasaserumproteinwithnecrotizingeffectsoncertaintransplantablemousetumorsinvivoandcytotoxiceffectsagainstsometransformedcellsinvitro.TheTNFfamilyconsistsoftwoproteinsdesignatedTNF-alpha,alsocalledcachectin,andTNF-beta,alsocalledlymphotoxin,whicharepleiotropiccytokinesthatcanmediateawidevarietyofBIOLOGicaleffects.TNF-betaisproducedbyactivatedlymphocytes,whereasTNF-alphaismostlyproducedbyactivatedmacrophages.SolubleTNF-betaisaT-cellderivedglycoproteinof25kD.TNF-betaisinducedinanantigen-specificMHCrestrictedfashionfromclassIandclassIIrestrictedTcells.ViralinfectionisalsoassociatedwithTNF-betaproductionbylymphoidcells.TNF-betahasseveraleffectsontargetcellsincludingkilling,growthstimulation,inductionofadhesionmolecule(ICAM-1)expression,andinductionofdifferentiation.ThemechanismsofTNF-betaeffectsinvolvereceptorbindingandinternalizationandseveralsequelaeincludingchangesinprostaglandinsandchromosomeintegrity.TNF-betaparticipatesintumorimmunity,andithasbeenreportedtoinhibitcarcinogenesisaswellasgrowthofsometumorsinvivo.RecentstudieshavedemonstratedthatbothTNF-alphaandTNF-betaarecapableofactivatingneutrophilsinvitro.TheexposureofneutrophilstoTNF-alphaorTNF-betacausestheproductionofsuperoxiderADIcals,inducesphagocyticresponseandenhancesantibodydependentcellcytotoxicity.ThereleaseofIL-1fromhumanendothelialcellsisalsoinducedbyTNF-alphaandTNF-beta.AlltheinvitrostudiessuggestthatTNF-betamayplayanimportantroleinimmunoregulation.InfibroblastsTNF-betainducesthesynthesisofcolony-stimulatingfactors,IL-1,Collagenaseandprostaglandin-E2.Monocytesarestimulatedforterminaldifferentiation.OnB-cellsTNF-betaactsasmitogen.AsTNF-betaexertsproliferativecapacityonfibroblastsitmayparticipateintheprocessofwoundhealing.WhilebothTNFsinhibitgrowthoftumorcells,theystimulatethegrowthofhumanlungfibroblastsanddermalfibroblasts.TNF-betaalsoactsasantiviralagentagainstavarietyofRNA(VSVandEMCV)andDNA(Ad-2andHSV-2)virusesanditsactivityispotentiatedbyinterferongammainasynergisticfashion.Moreover,TNF-betacontributestothedefenseagainstparasiticinfectionsandinducesosteoclasticboneresorptionandinhibitionofbonecollagensynthesis.Theelucidationofthephysiologicalandpathophysiologicalrolewaslimitedduetoalackofadequateassaysystems.ThepresentassaydevelopedbyAdolfandLamcheprovidesasimpleandrapidmethodfordeterminationofserumlevelsofTNF-betawithaminimaldetectabledoseaslowas7pg/mlserum.ThisassaywillhelptoclarifythepossIBLediagnosticandprognosticvalueofcirculatingTNF-betainvariousneoplasticandinflammatorydiseases.Theassaydetectsrecombinant,unglycosylatedlymphotoxinwiththesamesensitivityasthenatural,glycosylatedprotein,showsgoodcorrelationwiththestandardcytotoxicitybioassay,andisspecificforbiologicallyactiveTNF-betawithoutTNF-alphacrossreactivity.

Synonyms:Lymphotoxin,Tumornecrosisfactorligandsuperfamilymember1,LT-alpha