Inhibitory activity of interferons and interleukin 1 on the development of Plasmodium falciparum in human hepatocyte cultures.

We have studied the effect of natural and recombinant human interferons (HuIFN-alpha, -beta, and -gamma), and interleukin 1 (IL-1) on development of sporozoites of Plasmodium falciparum in cultures of functional hepatocytes. HuIFN-gamma inhibits hepatic schizogony of P. falciparum at very low concentrations (0.1 to 10 international units/ml), the target being the hepatocyte. Application after sporozoite inoculation is effective, suggesting an intracellular mechanism. There is also an 84% inhibition after application from 4 to 6 days following inoculation so that by day 6, there was a disappearance of a significant number of schizonts previously present at day 4, indicating more than a parasitostatic effect, and probably a postassembly action. HuIFN-alpha and -beta were effective, but only at 1000-fold higher concentrations than HuIFN-gamma. IL-1 (5 U/ml) also inhibited hepatic development of P. falciparum sporozoites; however, IL-1 treatment was effective only when applied before sporozoite inoculation.