Abstract
IL-15 has recently been detected in the synovium of patients with rheumatoid arthritis. IL-15-activated T cells induce significant TNF-alpha synthesis by macrophages via a cell contact-dependent mechanism, suggesting a key regulatory role for IL-15. Here, we report that the administration of a soluble fragment of IL-15Ralpha into DBA/1 mice, profoundly suppressed the development of collagen-induced arthritis. This was accompanied in vitro by marked reductions in Ag-specific proliferation and IFN-gamma synthesis by spleen cells from treated mice compared with control mice and in vivo by a significant reduction in serum anti-collagen Ab levels. These data directly demonstrate a pivotal role for IL-15 in the development of inflammatory arthritis and also suggest that antagonists to IL-15 may have therapeutic potential in rheumatic diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arthritis, Experimental / immunology*
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Arthritis, Experimental / pathology
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Arthritis, Experimental / prevention & control*
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Cell Line
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Collagen / administration & dosage
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Collagen / immunology*
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Drug Administration Schedule
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Epitopes, T-Lymphocyte / immunology
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Immunosuppressive Agents / administration & dosage*
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Immunosuppressive Agents / chemical synthesis
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Injections, Intradermal
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Injections, Intraperitoneal
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Interleukin-15 / metabolism
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Interleukin-15 / physiology*
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Male
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Mice
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Mice, Inbred DBA
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Peptide Fragments / administration & dosage
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Peptide Fragments / biosynthesis
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Peptide Fragments / genetics
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Receptors, Interleukin-15
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Receptors, Interleukin-2 / administration & dosage*
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Receptors, Interleukin-2 / biosynthesis
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Receptors, Interleukin-2 / genetics
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / biosynthesis
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Solubility
Substances
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Epitopes, T-Lymphocyte
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Il15ra protein, mouse
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Immunosuppressive Agents
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Interleukin-15
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Peptide Fragments
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Receptors, Interleukin-15
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Receptors, Interleukin-2
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Recombinant Proteins
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Collagen