In vivo protection against interleukin-1-induced articular cartilage damage by transforming growth factor-β1: Age-related differences

Abstract

Objectives - Transforming growth factor-β (TGF-β) has been shown to antagonise interleukin-1 (IL-1) effects in different systems. Investigations were carried out to study whether TGF-β1 modulates IL-1 induced inflammation and IL-1 effects on articular cartilage in the murine knee joint. Methods - IL-1, TGF-β1 or both factors together were injected into the knee joint. Inflammation was studied in whole knee histological sections. Patellar cartilage proteoglycan synthesis was measured using 35S-sulphate incorporation while patellar cartilage glycosaminoglycan content was determined with automated image analysis on joint sections. Results - Co-injection of TGF-β1 and IL-1 resulted in synergistic attraction of inflammatory cells. In contrast, TGF-β1 counteracted IL-1 induced suppression of articular cartilage proteoglycan synthesis. Proteoglycan depletion was similar shortly after the last injection of IL-1 or IL-1/TGF-β1, but accelerated recovery was found with the combination at later days. This protective effect of TGF-β1 could not be demonstrated in older mice. Conclusions - GF-β1 aggravates IL-1 induced knee joint inflammation. but counteracts the deleterious effects of IL-1 on articular cartilage proteoglycan synthesis and content. The data indicate that TGF-β1 could play an important part in articular cartilage restoration after IL-1 induced proteoglycan depletion.