Objective. Joint bleeding, or hemarthrosis, leads in time to severe joint damage. This study was carried out to test the in vitro thresholds of exposure time and concentration that lead to irreversible joint damage, to add to the discussion on the usefulness of aspiration of the joint after a hemorrhage.Methods. Explants of healthy human articular cartilage tissue were cultured in the presence or absence of 50% (volume/volume) blood for 1, 2, 3, or 4 days or in the presence of 0%, 5%, 10%, 20%, 30%, or 50% (v/v) blood for 4 days, followed by a 12-day period of recovery after withdrawal of blood. The effect of blood exposure on cartilage was determined by measuring the rate of proteoglycan synthesis as well as the release and content of cartilage matrix proteoglycans and the activity of matrix metalloproteinases.

SummaryHaemophilic arthropathy is joint damage evolving from recurrent joint bleeds that occur in patients suffering from the clotting disorder haemophilia. Insight into the pathogenetic mechanism of this blood-induced arthropathy yields possible treatment targets and modalities useful to reduce this invalidating co-morbidity of haemophilia. Joint bleeding leads to initially independent adverse changes in both the synovial tissue and the articular cartilage. These subsequently influence each other: the synovial inflammatory changes enhancing cartilage damage and vice versa. Consequently, effective treatment strategies will have to affect both pathways.

Objective: It has been reported that interleukin (IL)-10 limits blood-induced cartilage damage. Our aim was to study the effect of IL-4 alone and in combination with IL-10 on blood-induced cartilage damage. Design: Healthy human full thickness cartilage explants were cultured for 4 days in the presence of 50% v/v blood. IL-4, IL-10, or a combination of both cytokines was added during blood exposure. Cartilage matrix turnover was determined after a recovery period; additionally cytokine production, chondrocyte apoptosis, and expression of the IL-4 and IL-10 receptors were analyzed directly after exposure. Results: Blood-induced damage to the cartilage matrix was limited by IL-4 in a dose-dependent way (P < 0.05). Also IL-10 limited this damage, although to a lesser extent (P < 0.03). The effect of IL-4 plus IL-10 was more pronounced and protective than IL-10 alone (P < 0.05). Production of IL-1b and tumor necrosis factor (TNF)-a was limited by both IL-4 and IL-10 (P < 0.05), but more strongly by IL-4. Bloodinduced apoptosis of chondrocytes was limited by IL-4 and the combination, and not by IL-10 alone. No direct beneficial effect of IL-4 or IL-10 on cartilage was found, however, the chondrocyte receptor expression of both cytokine receptors was upregulated by exposure to blood. Conclusions: This study demonstrates that IL-4 alone and in combination with IL-10 prevents bloodinduced cartilage damage. Expectedly, anti-inflammatory effects on monocytes in the blood fraction and protective effects on chondrocytes are both involved. IL-4 in combination with IL-10 might be used to prevent blood-induced joint damage as a result of trauma or surgery.

Summary Despite prophylactic treatment, haemophilia patients suffer from spontaneous joint bleeds, which lead to severe joint damage. Also after joint trauma, an intra‐articular haemorrhage can add to joint damage over time. This study evaluated interleukin 10 (IL‐10) in the search for possible interventions to prevent or limit the damaging effects of joint bleeds. Human articular cartilage tissue explants were cultured in the presence or absence of 50% v/v blood (or its cellular components) for 4 d (the expected blood load in vivo after a joint haemorrhage), followed by a recovery period of 12 d. Pharmacological dosages of IL‐10 reached during treatment (1 or 10 ng/ml) were added. Additionally, cartilage and synovial tissue obtained from joints with end‐stage haemophilic arthropathy (HA) were cultured in the presence of IL‐10 (10 ng/ml). IL‐10 protected cartilage from the damaging effects of blood exposure, measured by its effects on proteoglycan turnover. In addition, IL‐10 beneficially influenced cartilage from patients with HA and reduced the production of the inflammatory cytokines IL‐1β and tumour necrosis factor‐α by haemophilic synovial tissue. Taken together, although effects were obtained in vitro, IL‐10 protects against blood‐induced joint damage and might be further evaluated as candidate in treatment of tissue damaging effects of joint haemorrhages.