Pathogenesis of inflammation. Effects of the pharmacological manipulation of arachidonic acid metabolism on the cytological response to inflammatory stimuli.
It is generally accepted that non-steroidal anti-inflammatory drugs (NSAIDs) act by the inhibition of prostaglandin biosynthesis. However, this hypothesis may not apply to all NSAIDs at all doses. It has thus been proposed that, in high doses, NSAIDs counteract inflammation by the inhibition of the activity of inflammatory cells such as the neutrophil. Neutrophils are activated by a 'twin signal' which is a part of a general stimulus response coupling mechanism involving phospholipid remodelling. This 'twin signal' consists of the mobilisation of intracellular calcium and the activation of protein kinase C. NSAIDs inhibit the aggregation of neutrophils in vivo and in vitro, and show additive effects with stable prostaglandins on the inhibition of the generation of superoxide anion, a product of inflammation. Binding studies have shown that the mechanism of this effect appears to be an interference with the ligand-receptor site modulated by the G protein. Activation of the cells of the marine sponge, which are not responsive to stable prostaglandins and do not contain a cyclo-oxygenase, can be inhibited by NSAIDs. Therefore, further investigation of this interesting hypothesis should help to clarify the precise mechanism of the anti-inflammatory effects of these drugs.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism*; D002449:Cell Aggregation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; C029152:G-substrate; D009419:Nerve Tissue Proteins; D010743:Phospholipids; D011453:Prostaglandins; D011956:Receptors, Cell Surface; D013481:Superoxides