Intra-articular administration of interleukin-1 causes prolonged suppression of cartilage proteoglycan synthesis in rats.
The effect of IL-1 on proteoglycan synthesis was studied after intraarticular injection of IL-1 into the knee joints of rats. IL-1 reduced the sulfated glycosaminoglycan synthesis in the articular cartilage of rats in a dose-dependent fashion. Analysis of the sulfated molecules by chondroitinase ABC digestion followed by composite agarose/acrylamide gel electrophoresis confirmed the proteoglycan nature of the molecules. Immunoprecipitation of the methionine-labeled extracts with a polyclonal antibody against the core protein indicated that the reduction in glycosaminoglycan synthesis was due to an inhibition of the core protein synthesis after IL-1 treatment. IL-1 induced inhibition occurred in both young and old rats and was independent of the prostaglandin pathway, as non-steroidal anti-inflammatory drugs failed to block the inhibition of proteoglycan synthesis by IL-1. The cartilage of rats injected with IL-1 was able to recover with time and synthesize normal amounts of total proteoglycan. However, administration of successive doses resulted in a much delayed return to normal synthesis. These results suggest that IL-1, if available locally in a cyclical fashion, could significantly interfere with the ability of cartilage to repair by causing a prolonged suppression of proteoglycan synthesis.
Chandrasekhar
S
S
Skeletal Diseases Research Group, Lilly Research Laboratories, Indianapolis, IN 46285.
Harvey
A K
AK
Hrubey
P S
PS
D000367:Age Factors; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D003864:Depression, Chemical; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000096:biosynthesis; D007249:Inflammation; D007270:Injections, Intra-Articular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007717:Knee; D008297:Male; D014176:Protein Biosynthesis; D011509:Proteoglycans / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006025:Glycosaminoglycans; D007375:Interleukin-1; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha