Combination Effects of Prednisolone and Interleukin-4 Protect Bovine Nasal Cartilage Explants from Interleukin-1α Induced Degradation

Background: Current treatments for joint diseases are moderately successful, but unfortunately are associated with significant side effects. This study was undertaken to investigate the combination effects of IL-4 and prednisolone on tissue characteristics and production of matrix metalloproteinase-1(MMP-1) in IL-lα-treated bovine nasal cartilage (BNC) explants. Methods: BNC explants were cultured in DMEM with IL-lα (10 ng/ml), IL-4 (50 ng/ml) and prednisolone (1 or 1,000 nM) at the same time for 28 days. At days 3, 7, 14, 21and 28, the media were collected and replaced with fresh media, and the removed media were stored at -20°C. The alterations of tissue characteristics were assessed by using histology techniques. Western-blot method was used to determine the effects of IL-4 and prednisolone combination on MMP-1 production. The cell viability was evaluated by using lactate dehydrogenase assay test. Results: In the presence of IL-lα alone, most chondrocytes were transformed into fibroblast-like morphology with pyknotic nuclei at day 28. In addition, a clear band of MMP-1 and extracellular matrix (ECM) degradation were observed. In combination of IL-4 and prednisolone, chondrocytes preserved their ordinary normal features. MMP-1 band formation was completely inhibited and ECM absolutely showed normal characteristics. IL-4 and prednisolone did not show cytotoxicity effects on BNC explant culture. Conclusion: This combination can strongly preserve cartilage from degradation features and the data possibly suggest that the combination of IL-4 and prednisolone could be a candidate for alternative therapy in joint diseases.