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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-3-20
pubmed:abstractText
Interleukin-1 receptor antagonist (IL-1Ra) is a natural IL-1 inhibitor, which competitively inhibits binding of IL-1 to its receptors. IL-1Ra is produced as four different isoforms, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, 2, 3), derived from the same gene. We previously observed increased production of icIL-1Ra1 in the joints of mice with collagen-induced arthritis (CIA). However, due to its intracellular localization, the biological role of icIL-1Ra1 remains unknown. The aim of the present study was to examine the effect of the icIL-1Ra1 isoform, as compared to that of sIL-1Ra, in the CIA model by comparing transgenic (tg) mice overexpressing icIL-1Ra1 or sIL-1Ra to their wild-type littermates. Serum levels of tg human IL-1Ra were elevated in sIL-1Ra and, to a lesser extent, also in icIL-1Ra1 mice. Clinical scoring indicated that none of the icIL-1Ra1 or siL-1Ra tg mice developed CIA, whereas arthritis was present in, respectively, 60% and 100% of their wild-type littermates. Histological and radiological analyses confirmed the absence of arthritis in icIL-1Ra1 and sIL-1Ra tg mice. Accordingly, circulating levels of the acute-phase protein serum amyloid A tended to be lower in icIL-1Ra1 tg mice than in their wild-type littermates and were significantly lower in sIL-1Ra tg mice than in controls. In contrast, no difference was observed between the groups regarding serum levels of anti-type II collagen antibodies and ex vivo spleen cell proliferative response to collagen. In conclusion, icIL-1Ra1, which is released into the extracellular space when produced in high amounts, has a similar anti-arthritic effect as sIL-1Ra.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
434-40
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Mice transgenic for intracellular interleukin-1 receptor antagonist type 1 are protected from collagen-induced arthritis.
pubmed:affiliation
Division of Rheumatology, University Hospital, Geneva, Switzerland.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't