Immunomodulatory effects of treatment with naproxen in patients with rheumatic disease

Abstract

We evaluated the effects of a nonsteroidal antiinflammatory drug, naproxen, on phytohemagglutinin (PHA)–induced lymphocyte proliferation. When added in vitro to cultures of peripheral blood mononuclear cells, naproxen enhanced the proliferative response toward PHA of lymphocytes from rheumatoid arthritis (RA) patients but not from healthy volunteers, and it reduced prostaglandin E2 (PGE2) synthesis in the cultures. Oral treatment for 7 days with naproxen also resulted in a significant enhancement of the in vitro PHA‐induced proliferation of lymphocytes from RA patients and from age‐matched control patients with noninflammatory rheumatic diseases, but not from young healthy controls. This enhancement of PHA‐induced lymphocyte proliferation after oral intake of naproxen was not accompanied by diminished in vitro PGE2 production in the cultures. It did occur when PGE2‐producing monocytes were removed and when in vitro PGE2 synthesis was blocked with indomethacin. We conclude that oral treatment with naproxen has an immunomodulatory effect and improves in vitro PHA‐induced proliferation of lymphocytes from rheumatic disease patients. This effect is not due to reduced PGE2 synthesis in the in vitro cultures, but reflects a more fundamental in vivo change in immunoregulation.

Increase in okm1 + granular lymphocytes in patients with rheumatoid arthritis

“…In a recent study, RA patients and controls were reported to have increased PHA responsiveness following the administration of the NSAID naproxen (29). Similar findings have been previously described in RA patients treated with piroxicam (13).…”

Variations in response to non‐steroidal anti‐inflammatory drugs.

“…It has become apparent that NSAIDs have considerable actions on the immune response and some of these actions may not be due to the inhibition of prostaglandin synthesis (Cueppens et al, 1986).…”

“…A small number of studies have examined the pharmacokinetics of NSAIDs in 'responder' and 'non-responder' groups of subjects. It has become apparent that NSAIDs have considerable actions on the immune response and some of these actions may not be due to the inhibition of prostaglandin synthesis (Cueppens et al, 1986).…”