Effects of diclofenac, indomethacin, tolfenamic acid and hydrocortisone on prostanoid production in healthy and rheumatic synovial cells.

Prostanoids, found in enhanced concentrations in rheumatic synovial fluid, are involved in the joint destruction seen in rheumatoid arthritis. Adherent cells isolated from rheumatic synovia produce higher amounts of prostanoids in a primary cell culture than cells originating from non-inflamed synovia. In the present study, it was found that exogenous arachidonic acid diminished the differences in prostanoid production between healthy and rheumatic synovial cells. Non-steroidal anti-inflammatory analgesics in clinically relevant concentrations had similar inhibitory effects on arachidonic acid-stimulated prostanoid synthesis in both healthy and rheumatic cells. In the presence of exogenous arachidonic acid, hydrocortisone (0.3-5.0 microM) did not affect prostanoid production in healthy cells. In rheumatic synovial cells hydrocortisone reduced PGE2 and PGF2 alpha synthesis to about half of the control value and the effect was not reversed by adding excess exogenous arachidonic acid. Altered regulation of phospholipase A2 activity in rheumatic synovia could explain the observed differences between healthy and rheumatic synovial cells.