Present status and new perspectives in non-steroidal anti-inflammatory drugs therapy

The mere mechanism of inhibition of synthesis of prostaglandins (PGs) is unable to account for the whole anti-inflammatory activity of non-steroidal anti-inflammatory drugs (NSAIDs). In fact most of them have been found to inhibit, to a varying degree from drug to drug, some polymorphonuclear (PMN) functions, namely their aggregation, superoxide anion generation, lysosomal enzyme release and, in addition the production of leukotriene B4, which induces an intense inflammatory response. The observation that some patients with chronic inflammatory arthropathies on treatment with NSAIDs undergo an impressive clinical remission together with the reduction of inflammation indices in plasma is sustained by many in vitro and in vivo experiences, where different NSAIDs have been found able to influence the behaviour of the immune system cells and of the para-immune one (PMNs and macrophages). A support mechanism might be through an inhibition of IL-1 synthesis. Furthermore the aspect of the "responders" and "non-responders" subjects is reviewed in the light of new knowledge of the problem of the rate of racemate of the administered NSAID, of the unbound plasma fraction of a given NSAID, of the relevance of the entero-hepatic recirculation etc. Anyway, the unpredictable range of inter-disease variability of response to NSAIDs from the clinical standpoint remains to be explained; it could be due to different pathogenic mechanisms acting in the relative diseases. Finally possible perspectives of development of new NSAIDs are put forward.