Benoxaprofen activation of suppressor activity in mononuclear leucocytes by a pro-oxidative mechanism in vitro

The effects of benoxaprofen on spontaneous and concanavalin A-induced suppressor activity in human mononuclear leucocytes (MNL) were assessed in vitro. The drug was used at a fixed concentration of 10(-4) M (30 micrograms/ml) in these studies. Benoxaprofen-treated MNL suppressed the responsiveness of untreated autologous MNL to the mitogen phytohaemagglutinin and potentiated the induction of suppressor activity in MNL by concanavalin A. Benoxaprofen at the same concentration increased MNL oxidative metabolism measured by chemiluminescence. Inclusion of the anti-oxidants ascorbate or cysteine (1 X 10(-3) M) in the assay system or depletion of adherent cells from MNL populations was associated with the elimination of both benoxaprofen-mediated suppression and increased MNL oxidative metabolism. Benoxaprofen per se was not an oxidizing agent nor did the drug possess peroxidase-like properties. These findings show that benoxaprofen induces suppressor activity in MNL by a pro-oxidative mechanism dependent upon intact cellular oxidative metabolism. Induction of suppressor activity in MNL by pro-oxidative drugs may be an important anti-inflammatory mechanism.