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.