Evidence for the involvement of interleukin 1 in human osteoarthritic cartilage degradation: protective effect of NSAID.
Our study demonstrates for the first time the presence, in situ, of interleukin 1 (IL-1) in human osteoarthritic (OA) synovium as well as in cartilage. In vitro IL-1 was found to significantly increase the catabolism of proteoglycan macromolecules and to stimulate the metalloprotease activity in human OA cartilage explants. Tiaprofenic acid, a nonsteroidal antiinflammatory drug belonging to the propionic acid class, reduced both the proteoglycan catabolism (26 micrograms/ml, 6.3 +/- 1.4%; 2.6 micrograms/ml, 7.1 +/- 1.4%) and metalloprotease activity (26 micrograms/ml, 1.1 +/- 0.3 units/mg wet weight; 2.6 micrograms/ml, 1.1 +/- 0.2 units/mg wet weight) induced by IL-1 (10.2 +/- 2.3%; 1.7 +/- 0.4 units/mg wet weight). The effect of tiaprofenic acid was reversed by a pharmacological dose of either PGE2 or dibutyryl cAMP.
Pelletier
J P
JP
University of Montreal, Notre-Dame Hospital Research Center, PQ, Canada.
Martel-Pelletier
J
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D046508:Culture Techniques; D000242:Cyclic AMP / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000517:prevention & control*; D011422:Propionates / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D011422:Propionates; D011509:Proteoglycans; D011994:Recombinant Proteins; C021270:tiaprofenic acid; D000242:Cyclic AMP; D008666:Metalloendopeptidases; D015232:Dinoprostone