Inhibition of human natural killer activity by cyclosporin A.

The effect of in vitro exposure to cyclosporin A on human natural killer (NK) activity was investigated using peripheral blood lymphocytes as effectors and 51Cr-labeled K562 cells as targets. After preincubation of the effectors with the drug for 20 hr, a dose-dependent reduction of NK activity was observed at concentrations ranging from 0.1 to 10 micrograms/ml. Exposure to the drug during the 20-hr preincubation and the 4-hr 51Cr-release assay resulted in greater impairment of NK cytotoxicity than preincubation alone, whereas the drug, present only during the assay, had no effect on cytolytic activity. Inhibition of NK activity required a minimal exposure time to the drug of 8 hr. The inhibitory effect of cyclosporin A on NK activity was rapidly reversible as, after a 20-hr incubation with 19 micrograms/ml, complete recovery of cytotoxicity was already observed after a further 4-hr culture in medium. Partially purified human fibroblast interferon augmented NK activity even in the presence of high concentrations (10 micrograms/ml) of cyclosporin A.