Enhanced prostaglandin E2 secretion by cytokine‐stimulated human synoviocytes in the presence of subtherapeutic concentrations of nonsteroidal antiinflammatory drugs

• Published in: Arthritis and rheumatism 1990-08, Vol.33 (8), p.1162-1169
• Main Authors: Lindsley, Herbert B., Smith, Donald D.
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Biological Factors - pharmacology; Bones, joints and connective tissue. Antiinflammatory agents; Cytokines; Dinoprostone - metabolism; Humans; Immunoenzyme Techniques; Indomethacin - pharmacology; Medical sciences; Microbial Collagenase - metabolism; Osmolar Concentration; Pharmacology. Drug treatments; Piroxicam - pharmacology; Sodium Salicylate - pharmacology; Synovial Membrane - cytology; Synovial Membrane - metabolism
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.1780330817

Human synoviocytes were stimulated for 48 hours or 72 hours with cytokines (recombinant interleukin‐1β and/or recombinant tumor necrosis factor α) in the presence or absence of selected nonsteroidal antiinflammatory drugs. The drugs were tested at subtherapeutic and clinically therapeutic levels, as follows: piroxicam 0.3 pM to 3 × 106 pM, sodium salicylate 30 nM to 3 × 106 nM, and indomethacin 3 pM to 3 × 106 pM. At low concentrations, all 3 drugs showed significant enhancement of prostaglandin E2 (PGE2) secretion (piroxicam, salicylate > indomethacin). At high, clinically therapeutic concentrations, all drugs showed suppression of PGE2 secretion (indomethacin > piroxicam > salicylate). The enhancement of PGE2 secretion may be partially responsible for the flare of arthralgia or arthritis frequently seen after termination of drug therapy.