|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0012634,
umls-concept:C0033684,
umls-concept:C0231491,
umls-concept:C0254610,
umls-concept:C0449258,
umls-concept:C0591833,
umls-concept:C0596988,
umls-concept:C0599894,
umls-concept:C0971858,
umls-concept:C1292733,
umls-concept:C1527148
|
|
pubmed:issue |
9
|
|
pubmed:dateCreated |
2004-10-20
|
|
pubmed:abstractText |
It has been suggested that the inflammatory cytokine IL-15 plays an important role in the development of several autoimmune diseases, including rheumatoid arthritis. We have generated a unique lytic and antagonistic IL-15 mutant/Fcgamma2a fusion protein (CRB-15) that targets the IL-15R. In the present study we examined the effects of targeting the IL-15R on the prevention and treatment of collagen-induced arthritis (CIA) in mice and probed the possible mechanisms of action of this IL-15 mutant/Fcgamma2a protein. Upon immunization with type II collagen, DBA/1 mice develop severe articular inflammation and destruction. Treatment of DBA/1 mice with a brief course of CRB-15 at the time of type II collagen challenge markedly inhibited the incidence and severity of arthritis. Moreover, in animals with ongoing established arthritis, treatment with CRB-15 effectively blocked disease progression compared with that in control-treated animals. The therapeutic effect of CRB-15 on either disease development or disease progression is remarkably stable, because withdrawal of treatment did not lead to disease relapse. A detailed analysis revealed that treatment with CRB-15 decreased synovitis in the joints; reduced bone erosion and cartilage destruction; reduced in situ production of the proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and IL-17; and decreased the responder frequency of autoreactive T cells. Our study suggests that the effective targeting of IL-15R-triggered events with CRB-15 can be of therapeutic importance in the treatment of rheumatoid arthritis.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Il15ra protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fc Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-15,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-15,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
0022-1767
|
|
pubmed:author |
pubmed-author:DonskoyElinaE,
pubmed-author:Ferrari-LacrazSylvieS,
pubmed-author:HancockWayne WWW,
pubmed-author:KimYon SuYS,
pubmed-author:LiXian ChangXC,
pubmed-author:MaslinskiWlodzimierzW,
pubmed-author:MollThomasT,
pubmed-author:NeubergManfredM,
pubmed-author:StromTerry BTB,
pubmed-author:ZanelliEricE,
pubmed-author:ZhengXin XiaoXX
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
173
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
5818-26
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:15494535-Animals,
pubmed-meshheading:15494535-Arthritis, Experimental,
pubmed-meshheading:15494535-Cell Migration Inhibition,
pubmed-meshheading:15494535-Collagen Type II,
pubmed-meshheading:15494535-Cytokines,
pubmed-meshheading:15494535-Disease Progression,
pubmed-meshheading:15494535-Gene Targeting,
pubmed-meshheading:15494535-Genetic Vectors,
pubmed-meshheading:15494535-Growth Inhibitors,
pubmed-meshheading:15494535-Immunoglobulin Fc Fragments,
pubmed-meshheading:15494535-Immunoglobulin G,
pubmed-meshheading:15494535-Incidence,
pubmed-meshheading:15494535-Inflammation Mediators,
pubmed-meshheading:15494535-Interleukin-15,
pubmed-meshheading:15494535-Male,
pubmed-meshheading:15494535-Mice,
pubmed-meshheading:15494535-Mice, Inbred DBA,
pubmed-meshheading:15494535-Mutagenesis, Site-Directed,
pubmed-meshheading:15494535-Receptors, Interleukin-15,
pubmed-meshheading:15494535-Receptors, Interleukin-2,
pubmed-meshheading:15494535-Recombinant Fusion Proteins,
pubmed-meshheading:15494535-Severity of Illness Index,
pubmed-meshheading:15494535-T-Lymphocyte Subsets
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Targeting IL-15 receptor-bearing cells with an antagonist mutant IL-15/Fc protein prevents disease development and progression in murine collagen-induced arthritis.
|
|
pubmed:affiliation |
Department of Medicine, Harvard Medical School, Division of Immunology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
