Production of prostanoids by rheumatic synovial cells in vitro: effects of anti-inflammatory drugs on arachidonic acid metabolism.
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 alpha and PGF2 alpha. 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 (greater than or equal to 0.13 mumol/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 alpha and PGF2 alpha 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 drugs in standardized cell culture conditions.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured; D015237:Dinoprost; D015232:Dinoprostone; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D011466:Prostanoic Acids / Q000378:metabolism*; D013583:Synovial Membrane / Q000187:drug effects*; D013929:Thromboxane B2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D005227:Fatty Acids; D011458:Prostaglandins E; D011460:Prostaglandins F; D011466:Prostanoic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D015232:Dinoprostone; D006854:Hydrocortisone