Abstract:

Some non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the production or actions of oxygen radicals generated by polymorphonuclear leucocytes (PMNs); this mechanism may contribute towards their anti-inflammatory activity. In the present study, the effects of a new enolcarboxamide NSAID, meloxicam, on oxyradical production by human PMNs exposed to various stimuli in vitro were compared with those of other standard NSAIDs. The various stimuli employed were intended to mimic the likely synergies which occur with cytokines and bacterial production (e.g. f-met-leu-phe (fMLP) peptide) in inflamed tissues and to give an insight into the site and mechanism of action of meloxicam and related drugs on the cellular processes involved in oxyradical generation. The results show that meloxicam is a potent inhibitor of oxyradical production at drug concentrations comparable with those encountered during therapy. Its mechanism of action appears similar to that of other enolcarboxamides and, while relatively complex, involves effects which are stimulus dependent and myeloperoxidase sensitive. They probably do not involve inhibition of fMLP-Gi protein receptor activation but may involve tumour necrosis factor-⇌ post-receptor activation. Enolcarboxamides have variable effects on phorbol myristate acetate-protein kinase C3-mediated oxyradical production.