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

Authors
  • Alexander, W S
  • Starr, R
  • Fenner, J E
  • Scott, C L
  • Handman, E
  • Sprigg, N S
  • Corbin, J E
  • Cornish, A L
  • Darwiche, R
  • Owczarek, C M
  • Kay, T W
  • Nicola, N A
  • Hertzog, P J
  • Metcalf, D
  • Hilton, D J
Type
Published Article
Journal
Cell
Publisher
Elsevier
Publication Date
Sep 03, 1999
Volume
98
Issue
5
Pages
597–608
Identifiers
PMID: 10490099
Source
Medline
License
Unknown

Abstract

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.

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