D. Jovanovic et al., EFFECT OF IL-13 ON CYTOKINES, CYTOKINE RECEPTORS AND INHIBITORS ON HUMAN OSTEOARTHRITIS SYNOVIUM AND SYNOVIAL FIBROBLASTS, Osteoarthritis and cartilage, 6(1), 1998, pp. 40-49
Objective: In this study we investigated the effect of interleukin-13
(IL-13), an anti-inflammatory cytokine, for potential therapeutic use
in osteoarthritis (OA). Design: We examined the effect of IL-13 on the
synthesis and expression of interleukin-1 beta (IL-1 beta), tumor nec
rosis factor-alpha (TNF-alpha), IL-1 receptor antagonist (IL-1Ra) and
stromelysin-1 on human OA synovial membrane in ex vivo cultures. In ad
dition, 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 recept
or binding, IL-1Ra and TNF-soluble receptors 55 and 75 (TNF-sR55 and T
NF-sR75). Results: In OA synovial membrane treated with LPS, IL-13 inh
ibited the synthesis of IL-1 beta, TNF-alpha and stromelysin-1. but in
creased 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 fibro
blasts, IL-13 decreased the level of IL-1 binding, an effect related t
o 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. Conclusion: These experiments suggest that IL-13 is potentially u
seful in the therapeutic treatment of OA, as it could regulate the maj
or pathological process of this disease by reducing the production of
proinflammatory cytokines and metalloproteases, and favoring the produ
ction of IL-1Ra.