Neutralization of interferon‐γ in neonatal SOCS1−/− mice prevents fatty degeneration of the liver but not subsequent fatal inflammatory disease

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Abstract
Mice lacking the suppressor of cytokine signalling-1 (SOCS1) die within weeks of birth with extensive fatty degeneration of the liver, consistent with acute hepatic toxicity to interferon-γ (IFN-γ), and inflammation of multiple organs. We show here that treatment for 1 week from birth with neutralizing antibody to IFN-γ rescues SOCS1−/− mice from lethal liver disease but the mice subsequently succumb to chronic inflammatory lesions characterized by T-lymphocyte infiltration of skeletal muscle, pancreas, lung, liver and skin. Elevated blood levels of eosinophils, neutrophils and platelets were also observed and the thymic lymphocyte population was depleted of CD4+ CD8+ T cells and showed a reduced CD4 : CD8 ratio. All T-cell populations in thymus, spleen and lymph node exhibited an increased proportion of cells bearing the activation marker CD44. These data suggest an important role for SOCS1 in T-lymphocyte regulation.