Effect of quinine and cinchonine on human neutrophils functions in vitro

We have compared the in-vitro interactions of quinine and cinchonine, two alkaloids from cinchona bark, with human neutrophil functions. Although these molecules are structurally similar, they induced a quantitatively different depressive effect on neutrophil chemotaxis and oxidative response. Quinine produced the strongest effect at concentrations as low as 10 mg/l, which may be achievable in serum during therapeutic use of this compound. The depression induced by cinchonine was noticeable only at 100 mg/l. Chemotaxis was decreased by about 25% (formyl-methionyl-leucyl-phenylalanine) or 39% (serum) for quinine (100 mg/l) only if a constant concentration of the drug was maintained during the assay while cinchonine had no effect on this PMN function. The greatest impairment was observed for the PMN oxidative burst: this was dose-dependent whatever the stimulus used (phorbol-myristate-acetate or opsonized zymosan). After 30 min incubation in the presence of the drugs, the zymosan-induced chemiluminescence response was decreased by 96% and by 67% with quinine, 100 and 10 mg/l, respectively, and by 62% with cinchonine 100 mg/l. The myeloperoxidase-mediated iodination of PMN was reduced by 100% and 46% with quinine, 100 and 10 mg/l, respectively, whereas cinchonine decreased this function by about 95% at 100 mg/l and 14% at 10 mg/l. Superoxide anion generation was impaired by 94% (quinine 100 mg/l) or 45% (cinchonine 100 mg/l). The relevance to the clinical situation and the possible mechanisms of such effects are discussed.