leukotriene-b4 and Chondrocalcinosis

The effects of sulfasalazine (SASP) and its metabolites sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) were investigated on release of prostaglandins (PG) and leukotrienes (LT) from synovial tissue of 37 patients with osteoarthritis, chondrocalcinosis and rheumatoid arthritis. Calcium ionophore A23187 significantly increased the release of PGE2, 6-keto-PGF1 alpha, LTB4, and LTC4 from human synovial tissue irrespective of the underlying joint disease. SASP inhibited release of LTC4 and increased release of PGE2. On the other hand, 5-ASA and SP inhibited the release of all eicosanoids measured. The effective concentrations of SASP and SP were found to be in the range which can be reached during SASP therapy. On the other hand, blood and synovial fluid levels of 5-ASA are considerably lower than those which inhibit eicosanoid synthesis in vitro. While nonsteroidal anti-inflammatory drugs, which are used for symptomatic therapy of rheumatoid arthritis, inhibit cyclooxygenase only, SP, the active metabolite of the second line anti-rheumatic drug SASP, inhibits both PG and LT release. Inhibition of LT synthesis by SASP and SP could contribute to the second line efficacy of SASP therapy in rheumatoid arthritis.

Topics: 6-Ketoprostaglandin F1 alpha; Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Chondrocalcinosis; Culture Techniques; Dinoprostone; Humans; Knee Joint; Leukotriene B4; Leukotrienes; Mesalamine; Osteoarthritis; Prostaglandins; SRS-A; Sulfapyridine; Sulfasalazine; Synovial Membrane