Soluble IL-15 receptor alpha-chain administration prevents murine collagen-induced arthritis: a role for IL-15 in development of antigen-induced immunopathology.
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.
Ruchatz
H
H
Department of Immunology and Centre for Rheumatic Diseases, University of Glasgow, United Kingdom.
Leung
B P
BP
Wei
X Q
XQ
McInnes
I B
IB
Liew
F Y
FY
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D003094:Collagen / Q000008:administration & dosage / Q000276:immunology*; D004334:Drug Administration Schedule; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000138:chemical synthesis; D007271:Injections, Intradermal; D007274:Injections, Intraperitoneal; D019409:Interleukin-15 / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010446:Peptide Fragments / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis; D012995:Solubility
D018984:Epitopes, T-Lymphocyte; C508025:Il15ra protein, mouse; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D010446:Peptide Fragments; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D003094:Collagen