197 INTERLEUKIN-10 PROTECTS AGAINST BLOOD-INDUCED JOINT DAMAGE

Abstract

Purpose: Joint bleeds occur frequently in patients suffering from haemophilia or can occur as a consequence of joint trauma or major joint surgery. Even a limited number of bleeds has been demonstrated to lead to severe joint damage in time. Small amounts of IL-1 that are produced by activated monocytes/macrophages as present within blood increase the production of hydrogen peroxide (H2O2) by chondrocytes. The hydrogen peroxide reacts with haemoglobin-derived iron from damaged and phagocytosed red blood cells in the joint cavity, which results in the formation of hydroxyl radicals in the vicinity of chondrocytes. This leads to chondrocyte apoptosis and with that the irreversible inhibition of cartilage matrix synthesis. This primary cartilage-driven joint damage is followed by synovial inflammation adding to joint damage. In search of possible interventions to prevent or limit the cartilage damaging effects of joint bleeds, we evaluated the potential of IL-10. Methods: Healthy human articular cartilage tissue explants were cultured in the presence or absence of 50% v/v blood for 4 days, followed by a recovery period of 12 days. IL-10 was added in 0.1, 1 or 10 ng/ml. Also cartilage and synovium in case of haemophilic arthropathy, obtained at joint replacement surgery, were cultured in the presence of IL-10 (10 ng/ml). The effect on cartilage matrix proteoglycan synthesis, -release, and -content were determined as well as the IL-1β and TNFα production by the synovium. Results: IL-10 was able to prevent dose dependently the decrease in proteoglycan synthesis and the increase in proteoglycan release of cartilage exposed to blood (p<0.05). As a consequence, the decrease in proteoglycan content after blood exposure could be prevented dose dependently (p<0.05). With 10 ng/ml IL-10, which is still a low dose for local therapeutic treatment, at least 50% reduction in adverse effects was observed (p<0.05). The matrix turnover of haemophilic cartilage improved upon addition of IL-10 and also the production of IL-1β and TNFα by haemophilic synovium decreased in the presence of IL-10 (all p<0.05). Conclusions: The present results show that interleukin-10 prevents the direct harmful effects of blood on articular cartilage and has a beneficial effect on the matrix turnover of haemophilic cartilage and pro-inflammatory cytokine production by haemophilic synovium. Therefore, although treatment studies in addition to prevention studies have to be performed; IL-10 might be worthwhile to test in clinical practice for local treatment of joint haemorrhages, to prevent joint damage in time.