LONG-TERM EFFECT OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON THE PRODUCTION OF CYTOKINES AND OTHER INFLAMMATORY MEDIATORS BY BLOOD-CELLS OF PATIENTS WITH OSTEOARTHRITIS

Most of the previous studies dealing with the effect of nonsteroidal a nti-inflammatory drugs (NSAIDs) on the synthesis of inflammatory media tors involved in joint damage have been done in cells cultured in vitr o or in blood cells from patients treated for short periods of time. I n this work we have evaluated the long-term effect of aceclofenac, a n ew NSAID, and diclofenac on the production of a series of inflammatory mediators by blood cells from 30 patients with severe knee osteoarthr itis. Both aceclofenac and diclofenac significantly inhibited prostagl andin E2 (PGE2) synthesis by blood mononuclear and polymorphonuclear c ells after 180 days of treatment. However, no clear effect was noted o n leukotriene B4 (LTB4) and platelet activating factor (PAF) productio n. The generation of O-2(-), by polymorphonuclear cells, stimulated wi th FMLP, was decreased after 15 days of treatment with both drugs, but reached normal values after 180 days. Interleukin-1 beta (IL-1 beta) production decreased significantly at 180 days with both drugs in the group of high producer patients. In a few (n = 3) patients with high b asal mononuclear cell tumor necrosis factor a (TNF alpha) production, this also decreased on treatment for 180 days with the NSAIDs. In the remaining low TNF alpha-producing patients, TNF alpha production tende d to increase. Interleukin-6 (IL-6) synthesis was not affected by acec lofenac while it was diminished by diclofenac. The decrease in IL-6 in all treated patients was significantly correlated with a worsening of the clinical condition. On the whole, these data could afford a patho genetic basis for the long-term employment of these drugs in patients with inflammatory conditions.