Mechanisms of Inflammation and Sites of Action of NSAIDs

Abstract

The mechanism of action of ibuprofen involves effects on various inflammatory mediators and cells involved in acute and chronic inflammation. Ibuprofen exists as two enantiomers: R(−) and S(+)-ibuprofen. R(−)-ibuprofen is metabolised by about 40–60% to the S(+) form which is an inhibitor of cyclo-oxygenase (COX)-1- and COX-2-derived prostaglandins (PGs). The production of PGs and COX-1-derived anti-platelet thromboxane A2 is related to its analgesic effects at OTC doses (<1,200 mg/day). R(−)-ibuprofen and its metabolism to S(+)-ibuprofen in leucocytes cause inhibition of production of enzymes and leukotrienes in these cells. Thus, ibuprofen has dual actions in controlling inflammation. The S(+) form is related to inhibition of PGs and the R(−) form related to its inhibitory effects on inflammatory leucocytes. Hence, there is a link of the metabolism of ibuprofen to its anti-inflammatory activity. Other actions of ibuprofen in inflamed tissues include inhibition of leucocyte accumulation and activation, oxyradicals, nitric oxide and enzymes and possibly pro-inflammatory cytokines all of which are involved in tissue and joint destruction in arthritic diseases. Anti-pyretic effects relate to inhibition of PG production in the hypothalamus as well as some peripheral effects on leucocytes.