Inhibition of phospholipase A₂ as a therapeutic target

The hydrolysis of cell membrane phospholipids by phospholipase A₂ (PLA₂) leads to the production of numerous lipid mediators of diverse pathological conditions, mainly inflammatory diseases. These include lysophospholipids and their derivatives, and arachidonic acid and its derivatives (the eicosanoids). Both these groups of mediators are produced predominantly by the secretory PLA₂s (sPLA₂s) which hydrolyze the phospholipids of the cell surface membrane. Protection of cell membrane from these 'inflammatory enzymes' can therefore be used for the treatment of inflammatory processes. A prototype of cell-impermeable PLA₂ inhibitors, which protect the cell membrane from different sPLA₂s without affecting vital phospholipid metabolism, is presented and discussed in the present review. (C) 2000 Elsevier Science B.V.