Effect of cyclosporin A on human neutrophil and monocyte function.

The effect of various concentrations of cyclosporin A (CyA), ranging from below peak blood levels to 20 times higher than blood levels of human peripheral blood polymorphonuclear and mononuclear leukocytes, was examined. CyA was found to bind to neutrophils with Kd values in the range of 20-50 nM. CyA at clinically obtainable blood level concentrations had no effect on neutrophil and monocyte chemotaxis, neutrophil oxidative burst, monocyte phagocytosis, or neutrophil bactericidal activity. The data on the release of lactoferrin, a secondary granule substance, from activated neutrophils showed that the calcium ionophore A 23187-induced lactoferrin release was inhibited by treatment of cells with 4 microM CyA, whereas release of lactoferrin from zymosan- or phorbol myristate acetate-activated neutrophils was not affected by the same concentration of CyA. This effect could either be due to differences in the degree of cell membrane perturbation by the various activators or to calcium dependence of neutrophil activation. A third possibility may be that CyA acts at some subsequent steps in the release process of neutrophils. It is concluded that CyA does not interfere with important functions of human phagocytes, the cells that play a major role in the defence against invading microorganisms.