Phospholipase A2 inhibitors in inflammation

The key reaction of the arachidonic acid cascade is the liberation of arachidonic acid from membrane phospholipids by a phospholipase A₂ (PLA₂). An excessive stimulation of this biochemical pathway leads to the formation of pathophysiological concentrations of lipid mediators like prostaglandins, leukotrienes, lysophospholipids and platelet activating factor, which are implicated in the development of inflammatory conditions. Thus, inhibitors of PLA₂ are expected to be a new treatment option for such diseases. One problem associated with the in vitro search for PLA₂ inhibitors is the selection of the appropriate enzyme, since many different PLA₂s are present in the mammalian organism. This paper discusses which of these PLA₂s is most likely to play the major role in the generation of the pro-inflammatory lipid mediators. Furthermore, patents claiming inhibitors of PLA₂s for the prevention and treatment of inflammation are reviewed for the period January 1997 to December 2000.