Effects of growth factors and cytokines on proteoglycan turnover in articular cartilage.
Proteoglycan biosynthesis was inhibited in a dose-dependent manner by the cytokines, interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha), in porcine articular cartilage in explant culture. These cytokines also increased the rate of degradation of proteoglycans. By contrast, the growth factors, insulin-like growth factor 1 (IGF-1) and transforming growth factor beta (TGF beta) had the opposite effect to the cytokines. When IL-1 and IGF-1 were added simultaneously, IGF-1 prevented the increase in matrix degradation caused by IL-1. Following IL-1 treatment of cartilage explants, recovery of proteoglycan synthesis was extremely slow, but could be greatly improved by addition of IGF-1 or TGF beta. Non-steroidal anti-inflammatory drugs (NSAIDs) had little effect on the recovery, but nor did they interfere with the action of IGF-1 and TGF beta. The local inflammatory effects of intra-articular injection of IL-1 into rabbit knee joints were blocked by intravenous administration of a recombinant IL-1 receptor antagonist, but similar treatment in antigen-induced arthritis did not prevent joint swelling, leucocyte infiltration or cartilage proteoglycan loss. The modulation of cytokine or growth factor actions may offer new strategies for limiting cartilage damage in joint diseases.
Hardingham
T E
TE
Kennedy Institute of Rheumatology, London, UK.
Bayliss
M T
MT
Rayan
V
V
Noble
D P
DP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D011817:Rabbits; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D017472:Receptors, Interleukin-1; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D006133:Growth Substances; D007375:Interleukin-1; D011509:Proteoglycans; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha