@article {Maneiro2692, author = {E Maneiro and M J L{\'o}pez-Armada and J L Fern{\'a}ndez-Sueiro and B Lema and F Galdo and F J Blanco}, title = {Aceclofenac increases the synthesis of interleukin 1 receptor antagonist and decreases the production of nitric oxide in human articular chondrocytes.}, volume = {28}, number = {12}, pages = {2692--2699}, year = {2001}, publisher = {The Journal of Rheumatology}, abstract = {OBJECTIVE: Interleukin 1 receptor antagonist (IL-1Ra) may play an important role in cartilage degradation by inhibiting IL-1 activity and therefore blocking IL-1 stimulation of prostaglandin E2 (PGE2) synthesis. Nitric oxide (NO) formation is increased during inflammation. High concentrations of NO exert negative effects on chondrocyte functions. We investigated the possible effects of 3 different nonsteroidal antiinflammatory drugs (NSAID; aceclofenac, piroxicam, aspirin) on IL-1Ra and NO production in human articular chondrocytes. METHODS: Normal and osteoarthritic (OA) cartilage samples were obtained from autopsy and prosthetic joint surgery, respectively. Chondrocytes were isolated and stimulated with 4 different stimuli: IL-1, tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and insulin-like growth factor (IGF). The 3 NSAID were added simultaneously to each different concentration of stimulus. IL-1Ra was measured in supernatant by ELISA; nitrites were quantified by the Griess reaction; PGE2 level was measured by enzyme immunoassay. RESULTS: OA samples spontaneously produced higher levels of IL-1Ra than normal samples (130+/-2.3 vs 30+/-3.1 pg/mI). IL-1, TNF-alpha, and LPS produced dose dependent increases in synthesis of IL-1Ra. In their presence, IL-1Ra was detected in supernatant at 48 h, but its highest level was measured at 144 h. The most potent stimulus was IL-1, followed by TNF-alpha. Fetal bovine serum and IGF in turn did not modify the basal levels of IL-1Ra. In contrast to piroxicam and aspirin, aceclofenac 10 microg/ml and TNF-alpha 10 ng/ml increased almost 46 times the basal amount of IL-1Ra produced by OA chondrocytes. Additionally, aceclofenac and aspirin inhibited NO synthesis. Finally, the 3 NSAID reduced the levels of PGE2 detected after stimulation with IL-1. CONCLUSION: Proinflammatory stimuli induce IL-IRa synthesis in human articular chondrocytes. Aceclofenac may modulate PGE2 production by increasing IL-IRa production and decreasing NO synthesis. Some NSAID exert diverse prostaglandin independent effects.}, issn = {0315-162X}, URL = {https://www.jrheum.org/content/28/12/2692}, eprint = {https://www.jrheum.org/content/28/12/2692.full.pdf}, journal = {The Journal of Rheumatology} }