M. Chabaud et al., IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis, ARTHRITIS R, 3(3), 2001, pp. 168-177
The origin and role of IL-17, a T-cell derived cytokine, in cartilage and b
one destruction during rheumatoid arthritis (RA) remain to be clarified. In
human ex vivo models, addition of IL-17 enhanced IL-6 production and colla
gen destruction, and inhibited collagen synthesis by RA synovium explants.
On mouse cartilage, IL-17 enhanced cartilage proteoglycan loss and inhibite
d its synthesis. On human RA bone explants, IL-17 also increased bone resor
ption and decreased formation. Addition of IL-1 in these conditions increas
ed the effect of IL-17. Blocking of bone-derived endogenous IL-17 with spec
ific inhibitors resulted in a protective inhibition of bone destruction. Co
nversely, intra-articular administration of IL-17 into a normal mouse joint
induced cartilage degradation. In conclusion, the contribution of IL-17 de
rived from synovium and bone marrow T cells to joint destruction suggests t
he control of IL-17 for the treatment of RA.