IL-4 alone and in combination with IL-10 protects against blood-induced cartilage damage

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-1 beta and tumor necrosis factor (TNF)-alpha was limited by both IL-4 and IL-10 (P < 0.05), but more strongly by IL-4. Blood-induced 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 blood-induced 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. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.