Effects of benoxaprofen on macrophage function (Abstract)
Benoxaprofen is a new non-steroidal anti-inflammatory drug which has been shown to have little cyclo-oxygenase inhibitory activity1 and to inhibit leucocyte migration (in vivo and in vitro)2,3. The effects of benoxaprofen in vivo on the chemotactic activity (CA) of inflammatory exudates have now been studied. In addition, the in vitro effects on phagocytosis by macrophages and on some of the accompanying biochemical events have been assessed. CA of 24 h pleural and peritoneal exudates from rats injected with glycogen or λ-carrageenin were evaluated. Oral administration of benoxaprofen reduced the levels of chemotaxins for macrophages in the exudates but had no significant effect on PMN migration. Phagocytosis by unelicited rat peritoneal macrophages of latex spheres was stimulated by benoxaprofen at low concentrations (1–10 μg/ml) but was reduced at 15 and 30 μg/ml by 20–25%. Stimulation of the hexose monophosphate (HMP) shunt during phagocytosis was inhibited by ~50% at 30 μg/ml and at lower concentrations in a dose related manner. Similar drug effects were seen on the HMP shunt stimulated by ascorbic acid. However, stimulation by Concanavalin A of the HMP shunt was potentiated by benoxaprofen at 30(μg/ml. Drug effects were partially reversed by washing the cultured cells. Benoxaprofen had no effect on the secretion or synthesis of β-glucuronidase by mouse macrophages after phagocytosis of serum treated zymosan particles.