Inhibitors of the leukocyte superoxide generating oxidase: mechanisms of action and methods for their elucidation.

Oxygen radical production by phagocytic cells is currently receiving a great deal of attention as the role of radical damage is becoming apparent in inflammatory diseases, reperfusion injury, cancer, and aging. A large number of inhibitors of the superoxide generating oxidase are known, including standard and experimental anti-inflammatory and anti-rheumatic drugs, natural products, anaesthetics, tranquillizers and antibiotics, in addition to compounds used as experimental tools. The composition of the oxidase and the possible sites of inhibition of these compounds are discussed together with the possible mechanisms of activation of the oxidase and the effects these agents may have on these pathways. Use of these compounds has provided a great deal of information about the components and the nature of the activation processes involved in the stimulation of radical production by leukocytes, as well as pointing to possible targets for the production of novel anti-inflammatory agents. It is clear however that further understanding of the precise nature of the activation pathways and the extent of the involvement of leukocyte-derived oxygen radicals in disease processes will require more specific inhibitors than most of those currently available.