Chloroquine and hydroxychloroquine inhibit multiple sites in metabolic pathways leading to neutrophil superoxide release.

The effect of chloroquine and hydroxychloroquine on human neutrophil polymorph superoxide (O2-) production stimulated either by opsonized zymosan, phorbol myristate acetate or fluoride was examined in vitro. Both drugs inhibited the response to all 3 stimuli in a dose and time dependent fashion. Inhibition of zymosan stimulated O2- release was only attributable in a minor degree to inhibition of expression of surface receptors (MO-1), and appeared to be mainly due to inhibitory effects on more distal components of the activation pathway. Possible mechanisms for the inhibition of fluoride and phorbol ester stimulated O2- release are discussed in the light of current understanding of metabolic pathways of neutrophil polymorph activation.