Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-8-16
pubmed:abstractText
Interleukin (IL)-18 is a potent stimulator of immunity and augments the severity of type II collagen-induced arthritis (CIA) in rats and mice by enhancing T helper 1 (Th1) cell activation, which increases the production of proinflammatory cytokines and arthritogenic antibodies. In this study, we show that recombinant IL-18 (rIL-18) also has a direct effect on normal rat chondrocytes maintained in vitro inducing them to produce proinflammatory factors including IL-6, regulated upon activation normal T cell expressed and secreted (RANTES), prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) in a dose- and time-dependent manner. The production of matrix metalloproteinase (MMP)-13, nitric oxide (NO), tumour necrosis factor (TNF)-alpha and IL-1beta were also enhanced, although less intensely. Neutralizing polyclonal anti-rIL-18 antibodies effectively blocked the production of IL-6, PGE(2) and RANTES, as well as mRNA expression for the same products in addition to IL-18 and TNF-alpha. In contrast, neutralizing antibodies to IL-1beta, TNF-alpha and IL-6 were ineffective in suppressing any of these products. Together, these findings suggest that IL-18 may play an important, possibly direct, role in mediating cartilage injury, which might not be amenable to treatment with currently utilized anti-cytokine agents. These findings suggest further that IL-18 antagonists might prove beneficial as anti-inflammatory and chondroprotective agents in the treatment of arthritis, and that the development of such agents for human use is worth consideration.
pubmed:grant
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0009-9104
pubmed:author
pubmed:issnType
Print
pubmed:volume
149
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
553-60
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
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