Cutting edge: Selective IL-18 requirements for induction of compartmental IFN-gamma responses during viral infection

Optimal protective effects for defense against infection require orchestrat ion of immune responses spanning multiple host compartments and divergent l ocal regulation at particular sites, During murine cytomegalovirus infectio ns known to target spleen and liver, IL-12-induced IFN-gamma from NK cells is crucial for resistance. However, the roles for IL-18 and/or IL-12 in reg ulating hepatic IFN-gamma responses, as compared with systemic or splenic r esponses, have not been defined. In this report, mice genetically deficient in either IL-18 or IL-12p35 exhibited up to 95% reductions in systemic and splenic IFN-gamma responses. Surprisingly, IFN-gamma responses were preser ved in the livers of IL-18-deficient, but not IL-12p35-deficient, mice. Cyt okine requirements for host survival also differed. Under conditions where mice lacking IL-12p35 exhibited 100% mortality, those lacking IL-18 survive d. Taken together, our results delineate contrasting compartmental requirem ents for IL-18 and suggest that preservation of local, hepatic IFN-gamma pr oduction is critical for host defense during murine cytomegalovirus challen ge.