SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine

Mice lacking suppressor of cytokine signaling-1 (SOCS1) develop a complex f atal neonatal disease. In this study, SOCS1(-/-) mice were shown to exhibit excessive responses typical of those induced by interferon gamma (IFN gamm a), were hyperresponsive to viral infection, and yielded macrophages with a n enhanced IFN gamma-dependent capacity to kill L. major parasites. The com plex disease in SOCS1(-/-) mice was prevented by administration of anti-IFN gamma antibodies and did not occur in SOCS1(-/-) mice also lacking the IFN gamma gene. Although IFN gamma is essential for resistance to a variety of infections, the potential toxic action of IFN gamma, particularly in neona tal mice, appears to require regulation. Our data indicate that SOCS1 is a key modulator of IFN gamma action, allowing the protective effects of this cytokine to occur without the risk of associated pathological responses.