マレイン酸プログルメタシンによるヒト好中球スーパーオキシド産生阻害

抄録

Polymorphonuclear leukocytes (PMN) play an important role in development of inflammation. In the clinical field, non-steroidal anti-inflammation drugs (NSAID), such as proglumethacin maleate, were used to theraphy with arthritis. In this study, we investigated the effects of NSAIDs on superoxide generation of human PMN from synovial fluid.
On the PMNs from synovial fluid of rheumatoid arthritis (RA) patients, proglumethacin maleate significantly inhibited the superoxide generation by phorbol 12-myristate 13-acetate (PMA) . The rate and maximum amount of superoxide generation of PMNs were reduced to 12.72±6.32% and 24.23±9.44%, respectively. The other NSAIDs, Indomethacin farnesil, diclofenac sodium and loxoprofen sodium, were also tended to inhibit the superoxide generation by PMA, but not significantly. Indomethacin farnesil, diclofenac sodium and loxoprofen sodium reduced the rate of superoxide generation to 55.88±5.58%, 41.17±2.36% and 45.24±1.77%, respectively. Proglumethacin maleate also strongly inhibited the superoxide generation of PMNs from patients of osteoarthritis (OA), but other NSAIDs did not. The rate and maximum amount of superoxide generation of PMNs from OA patients were reduced by proglumethacin maleate to 21.20±2.79% and 32.36±10.09%, respectively. Indomethacin which is active metabolite of proglumethacin maleate for NSAID did not inhibit the superoxide generation of PMNs from RA and OA patients.
These result indicated that proglumethacin maleate have inhibitory action to superoxide generation of PMNs which is not NSAID's action. This inhibition of superoxide generation of PMNs may be one of the anti-inflammatory mechanisms of proglumethacin maleate.