TumorNecrosisFactor(TNF)wasoriginallydiscoveredinseraofanimalsandwasfoundtocausehemorrhagicnecrosisofsometransplantablemouseandhumantumorsandtoexhibitprimarily
cytotoxicactivitiesagainsttumorbutnotnormalcellsinvitro.TheTNFfamilyconsistsoftwoproteinsdesignatedTNF-alpha,alsocalledcachectin,andTNF-beta,alsocalledlymphotoxin,whicharepleiotropiccytokinesthatcanmediateawidevarietyofBIOLOGicaleffects.
BothTNF-alphaandTNF-betahavebeenshowntointeractwithacellthroughspecifichighaffinityreceptorswithafewhundreduptomorethan20,000copiespercell.TNF-receptorshave
beendemonstratedonawidevarietyofhumansomaticcellsincludingfibroblasts,endothelialcells,ADIpocytes,livermembranes,granulocytesandseveraltumorcelllines.Normalandmalignanthumanmyeloidcellsaswellasmitogen-stimulatedlymphocytesexpresssimilarnumbersofTNFreceptors(400-1,900percell),whereasrestinglymphoidcellshavefewer,redbloodcellsandplateletshavenodetectableTNFreceptors.InmostcasesnocorrelationisobservedbetweenreceptornumberandsensitivitytoTNF.Basedongelfiltrationexperimentsthereceptorappearstobeacomplexofdifferentproteinswithamolecularweightof350kDa.InavarietyofcelllinestwodifferenttypesofTNFreceptorswith75-80and55-60kDarespectivelyhavebeenidentified.Thepresentassayprovidesasimple,rapidandhighlysensitivemethodforthedeterminationofsolubleTNF-R(80kDa)levelsinbodyfluidsorcellculturesupernatants.ThisassaywillhelptoclarifythepossIBLediagnosticandprognosticvalueofcirculatingsTNF-R(80kDa)invariousneoplasticandinflammatorydiseases.

-autoimmunediseases:inpatientswithsystemiclupuserythematosus(SLE)andprogressivesystemicsclerosis(PSS),plasmaconcentrationsofbothtypesofTNFreceptorsandinmixed
connectivetissuesdisease(MCTD)patients,typeTNF-R(80kDa)receptorsaresignificantlyelevatedcomparedtocontrols.Inrheumatoidarthritispatients,concentrationsofTNF-R(60kDa)andTNF-R(80kDa)aresignificantlyhigherthanincontrols.

-hematology:upregulationofTNF-Risfoundinreactivehyperplasia.ExpressionofTNF-Rismainlyseeninhigh-grademalignantNon-Hodgkin`slymphoma.Concentrationsofthe60kDatypesTNF-RaresignificantlyhigherinHodgkin´sDiseasepatientsthaninhealthycontrols.

-HIV:sTNF-RisupregulatedfollowingSEROconversion,remainspersistentlyhighduringtheasymptomaticphaseandbecomesevenmoreelevatedinsomeARCandAIDSpatients.

-kidney:sTNF-Riselevatedinserumandurineofpatientsonchronichemodialysis.Thismayhavebeneficialeffectsoninflammatoryconditions.

-liver:differentialdiagnosisofascites:sTNF-Rlevelsinascitesaresignificantlyelevatedinpatientswithmalignancy-relatedandinfectedascitescomparedwithpatientswithuncomplicatedhepaticascites.

-Malaria:theexcessivereleaseofTNFinducedbymalariaparasitesiscontrolledbysTNF-RthatbindsanddeactivatesTNF.

-ovary:elevatedlevelsofsTNF-RinhibitthecytolyticactivityofrecombinantTNFgiveninthecourseofimmunotherapy.

-pancreas:humanpancreaticcarcinomacellsexpressreceptorsforTNF.ElevatedsTNF-Rlevelsmaythereforebeofprognosticvaluefordetectionofpancreaticcarcinoma.(31)

-pregnancy:sTNF-Rlevelsareaphysiologicconstituentofamnioticfluid(AF).ElevationsofsTNF-RlevelsinAFaredirectlyrelatedtointrauterineinfectionandpretermparturition.

-skin:sTNF-Rissignificantlyelevatedinpatientswithsevereburns.

-therapy:recombinantTNFasacancertherapeuticcanprovokereleaseofsTNF-R.