Neutralization of interferon-gamma in neonatal SOCS1(-/-) mice prevents fatty degeneration of the liver but not subsequent fatal inflammatory disease

Mice lacking the suppressor of cytokine signalling-1 (SOCS1) die within wee ks of birth with extensive fatty degeneration of the liver, consistent with acute hepatic toxicity to interferon-gamma (IFN-gamma), and inflammation o f multiple organs. We show here that treatment for 1 week from birth with n eutralizing antibody to IFN-gamma 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, lu ng, liver and skin. Elevated blood levels of eosinophils, neutrophils and p latelets were also observed and the thymic lymphocyte population was deplet ed 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 propor tion of cells bearing the activation marker CD44. These data suggest an imp ortant role for SOCS1 in T-lymphocyte regulation.