Effect of IL-13 on cytokines, cytokine receptors and inhibitors on human osteoarthritis synovium and synovial fibroblasts.
OBJECTIVE
In this study we investigated the effect of interleukin-13 (IL-13), an anti-inflammatory cytokine, for potential therapeutic use in osteoarthritis (OA).


METHODS
We examined the effect of IL-13 on the synthesis and expression of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-1 receptor antagonist (IL-1Ra) and stromelysin-1 on human OA synovial membrane in ex vivo cultures. In addition, we explored the effect of IL-13 on both the IL-1 receptor (IL-1R) and TNF-receptor (TNF-R) systems on OA synovial fibroblasts. This included determination of the levels of IL-1 beta and TNF-alpha receptor binding, IL-1Ra and TNF-soluble receptors 55 and 75 (TNF-sR55 and TNF-sR75).


RESULTS
In OA synovial membrane treated with LPS, IL-13 inhibited the synthesis of IL-1 beta, TNF-alpha and stromelysin-1, but increased IL-1Ra production. In addition, IL-13 reduced the level of IL-1 beta mRNA and stimulated the level of IL-1Ra mRNA. In synovial fibroblasts, IL-13 decreased the level of IL-1 binding, an effect related to the increased production of IL-1Ra. Although IL-13 had no effect on the TNF-R level, this cytokine markedly decreased the shedding of TNF-R75.


CONCLUSIONS
These experiments suggest that IL-13 is potentially useful in the therapeutic treatment of OA, as it could regulate the major pathological process of this disease by reducing the production of proinflammatory cytokines and metalloproteases, and favoring the production of IL-1Ra.
Jovanovic
D
D
University of Montreal, Notre-Dame Hospital, L.C. Simard Center, Montreal, Quebec, Canada.
Pelletier
J P
JP
Alaaeddine
N
N
Mineau
F
F
Geng
C
C
Ranger
P
P
Martel-Pelletier
J
J
D000368:Aged; D015152:Blotting, Northern; D018929:Cell Culture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D018793:Interleukin-13 / Q000494:pharmacology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000187:drug effects; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000187:drug effects*; D012795:Sialoglycoproteins / Q000096:biosynthesis; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D018793:Interleukin-13; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D019278:Matrix Metalloproteinase 3