COX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease

A new generation of non-steroidal anti-inflammatory drugs has been describe d that selectively targets the inducible isoform of cyclo-oxygenase, cyclo- oxygenase 2 (COX-5). This isoform is expressed at sites of inflammation, wh ich has fed to the speculation that its inhibition could provide all the be nefits of current nonsteroidal anti-inflammatory drugs, but without their m ajor side-effects on the gastrointestinal system (which are due to inhibiti on of COX-1). We have shown that COX-2 (identified by use of specific antib odies) is induced during the resolution of an inflammatory response, inhibi tion of COX-2 resulting in persistence of the inflammation due to the preve ntion of the synthesis of a range of anti-inflammatory prostanoids. We prop ose that there is a third isoform of this enzyme family, COX-3, a proposal that will have implication for the prescription of both existing and new ge neration anti-inflammatory drugs, and might represent a new therapeutic tar get.