Production of prostanoids by rheumatic synovial cells in vitro: effects of anti-inflammatory drugs on arachidonic acid metabolism

Summary To evaluate the role of prostanoids in rheumatoid arthritis the effects of anti-inflammatory drugs on prostanoid concentrations and their ratios were studied in a primary culture of adherent synovial cells from patients with rheumatoid arthritis. Cells from rheumatoid synovium have a great capacity for prostanoid production. PGE₂ is the main prostanoid but synovial cells are also capable of producing 6-keto-PGF₁ and PGF₂. There were also very low TxB₂ concentrations in the culture medium after incubation. All nonsteroidal anti-inflammatory drugs used (diclofenac, indomethacin and tolfenamic acid) reduced markedly in concentrations achieved therapeutically (0.13 mol/l) the production of all the prostanoids from endogenous substrate. There were no differences in the efficacity of the drugs. Hydrocortisone was needed for higher concentrations to inhibit PGE₂, 6-keto-PGF₁ and PGF₂ production. TxB₂ formation remained almost unaltered. After the drug incubation there were also clear alterations in the ratios between these prostanoids, which may have therapeutic importance. It is suggested that this kind of synovial cell culture can be used for testing the effects and mechanisms of different anti-inflammatory drygs in standardized cell culture conditions.