IN-VIVO PROTECTION AGAINST INTERLEUKIN-1-INDUCED ARTICULAR-CARTILAGE DAMAGE BY TRANSFORMING GROWTH FACTOR-BETA(1) - AGE-RELATED DIFFERENCES

Objectives-Transforming growth factor-beta (TGF-beta) has been shown t o antagonise interleukin-1 (IL-1) effects in different systems. Invest igations were carried out to study whether TGF-beta 1 modulates IL-1 i nduced inflammation and IL-1 effects on articular cartilage in the mur ine knee joint. Methods-IL-1, TGF-beta 1 or both factors together were injected into the knee joint. Inflammation was studied in whole knee histological sections. Patellar cartilage proteoglycan synthesis was m easured using S-35-sulphate incorporation while patellar cartilage gly cosaminoglycan content was determined with automated image analysis on joint sections. Results-Co-injection of TGF-beta 1 and IL-1 resulted in synergistic attraction of inflammatory cells. In contrast, TGF-beta 1 counteracted IL-1 induced suppression of articular cartilage proteo glycan synthesis. Proteoglycan depletion was similar shortly after the last injection of IL-1 or IL-1/TGF-beta 1, but accelerated recovery w as found with the combination at later days. This protective effect of TGF-beta 1 could not be demonstrated in older mice. Conclusions-TGF-b eta 1 aggravates IL-1 induced knee joint inflammation, but counteracts the deleterious effects of IL-1 on articular cartilage proteoglycan s ynthesis and content. The data indicate that TGF-beta 1 could play an important part in articular cartilage restoration after IL-1 induced p roteoglycan depletion.