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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alphavirus Infections / mortality
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Alphavirus Infections / prevention & control
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Animals
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Carrier Proteins / physiology*
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Disease Susceptibility
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Gene Expression Regulation, Developmental*
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Interferon-gamma / antagonists & inhibitors*
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Interferon-gamma / pharmacology
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Interferon-gamma / physiology
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Leishmania major / immunology
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Leishmaniasis / mortality
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Leishmaniasis / prevention & control
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Lymphopenia / mortality
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Lymphopenia / prevention & control
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Macrophages / drug effects
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Repressor Proteins*
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Semliki forest virus / immunology
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Semliki forest virus / metabolism
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Signal Transduction*
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins
Substances
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Carrier Proteins
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Repressor Proteins
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Socs1 protein, mouse
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins
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Interferon-gamma