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

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