IL-18isapro-inflammatorycytokinesimilarinstructureandmechanismofactiontoIL-1beta.FormationofactiveIL-18bymacrophagesrequirescleavageofaninactiveprecursorbycaspase-1protease,alsotermedtheIL-1convertingenzyme(ICE).OneofthekeyBIOLOGicalresponsesinducedbyIL-18isthatincombinationwithIL-12itstimulatesTh1celldifferentiationandinvolvementinimmuneresponses.IL-18wasoriginallyknownasinterferon-gamma-inducingfactor,namedafteritsinductionofinterferon-gammaproduction.Up-regulationofFasligandinTh1cellsbyIL-18mayincreaseapoptosisofFasreceptorexpressingcellsthatinteractwiththeactivatedTh1cells.ThisinductionofapoptosismayallowIL-18tohaveanti-tumoractivityandmayalsoplayaroleinchronicinflammatoryandautoimmuneconditions. Contributor:GlennCroston,PhD. REFERENCES: