Cyclooxygenase-independent effects of non-steroidal anti-inflammatory drugs on the neutrophil respiratory burst.

A range of 12 non-steroidal anti-inflammatory drugs (NSAIDs), including members from each of the main chemical groups, were examined for their effects on the oxidative burst induced by the receptor stimulus, platelet-activating factor, and the two post-receptor stimuli, fluoride and dioctanoylglycerol. It was found that the NSAIDs fell into three categories: (1) those that increased the stimulated superoxide (O2-) response, (2) those that had no effect and (3) those that decreased O2- production. All the drugs were without effect in unstimulated cells. The mode of action of those drugs that caused enhancement of the O2- response is unlikely to be due to an inhibition of the cyclooxygenase pathway of arachidonate metabolism as not all NSAIDs caused the enhancement. This data could have clinical implications for the therapy of inflammatory disorders such as rheumatoid arthritis, in that those NSAIDs which cause an increased O2- response, while providing temporary relief of symptoms, could be exacerbating the underlying inflammatory condition and associated tissue damage.