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

Cell. 1999 Sep 3;98(5):597-608. doi: 10.1016/s0092-8674(00)80047-1.


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 gamma (IFNgamma), were hyperresponsive to viral infection, and yielded macrophages with an enhanced IFNgamma-dependent capacity to kill L. major parasites. The complex disease in SOCS1-/- mice was prevented by administration of anti-IFNgamma antibodies and did not occur in SOCS1-/- mice also lacking the IFNgamma gene. Although IFNgamma is essential for resistance to a variety of infections, the potential toxic action of IFNgamma, particularly in neonatal mice, appears to require regulation. Our data indicate that SOCS1 is a key modulator of IFNgamma action, allowing the protective effects of this cytokine to occur without the risk of associated pathological responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alphavirus Infections / mortality
  • Alphavirus Infections / prevention & control
  • Animals
  • Carrier Proteins / physiology*
  • Disease Susceptibility
  • Gene Expression Regulation, Developmental*
  • Interferon-gamma / antagonists & inhibitors*
  • Interferon-gamma / pharmacology
  • Interferon-gamma / physiology
  • Leishmania major / immunology
  • Leishmaniasis / mortality
  • Leishmaniasis / prevention & control
  • Lymphopenia / mortality
  • Lymphopenia / prevention & control
  • Macrophages / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Repressor Proteins*
  • Semliki forest virus / immunology
  • Semliki forest virus / metabolism
  • Signal Transduction*
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins


  • Carrier Proteins
  • Repressor Proteins
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Interferon-gamma