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SUMMARYThe effect of chloroquine and hydroxychloroquine on neutrophil superoxide release stimulated by the chemotactic tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) was examined. Both drugs caused time and dose dependent inhibition of superoxide release but had no effect on equilibrium binding of [3H]FMLP to its receptor. Preliminary experiments suggest that these drugs may exert their inhibitory effect on superoxide release by inhibiting the FMLP stimulated hydrolysis of phosphoinositides.Chloroquine (CQ), hydroxychloroquine (HCQ), and previously mepacrine have been widely used in the treatment of rheumatoid arthritis and systemic lupus erythematosus.1 They have both immunosuppressive and anti-inflammatory effects,' 2 which may be mediated by inhibition of polymorphonuclear (PMN) and mononuclear phagocyte function. 1 3 4 Both these cell types are intimately involved in the pathogenesis of inflammatory arthritis.Inhibitory effects of these drugs on phagocyte function have been attributed to their lysosomotropism, which results in inhibition of lysosomal functions, including lysosomal enzyme release, receptor recycling, lysosomal digestion, and metabolism of lipids.1 They also inhibit non-lysosomal functions, including cytokine release2 and chemotaxis.3 We have recently reported that these drugs have differential effects on other non-lysosomal aspects of blood monocyte metabolism and function, including superoxide production, phospholipid methylation, and arachidonic acid (AA) release.4 We have extended these studies to examine the effect of CQ and HCQ on PMN superoxide release stimulated by the chemotactic tripeptide, N-formyl-methionylleucyl-phenylalanine (FMLP).We report here that these agents inhibit FMLP stimulated superoxide release without affecting

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