Effects of some antimalarial drugs on rat inflammatory polymorphonuclear leukocyte function

In vitro concentrations of chloroquine, amodiaquine, quinine, and mefloquine were assessed with respect to functional responses (chemotaxis, anion superoxide generation, and lysosomal enzyme release) of rat polymorphonuclear leukocytes (PMN) collected after induction of acute pleural inflammation. Chloroquine, amodiaquine, and mefloquine exhibited dose-dependent inhibition of: (1) random migration and oriented migration of PMN; and (2) opsonized zymosan- or phorbol myristate acetate-stimulated PMN O2- release. These effects were not stimulus-specific and were largely reversed by washing the cells before stimulation Mefloquine was the most effective drug. Quinine had no effect on PMN migration. Apart from quinine, the drugs induced similar dose-dependent increases in beta-glucuronidase release from unstimulated PMN. Only quinine inhibited the enzyme release from stimulated PMN. Our data show that the antimalarial derivatives affect PMN functions in various ways and suggest that their effects reflect nonspecific modifications of cellular membrane.