The role of cytokines in malaria infection.

We have tested the prophylactic effect of Escherichia coli-derived recombinant human interferon gamma (rHuIFN-(gamma] against sporozoite- or trophozoite-induced Plasmodium cynomolgi B malaria infection in rhesus monkeys. Data show that treatment with only five doses of rHuIFN-(gamma) (0.1 mg/kg body weight) given on days -2, 0, and +2 after infection protected the monkeys against sporozoite-induced P. cynomolgi infection. Animals initially protected by rHuIFN-(gamma) treatment remained susceptible to reinfection. No inhibitory effect of rHuIFN-(gamma) was seen against trophozoite-induced infection. We have also tested the effect of recombinant human tumour necrosis factor (rHuTNF) in rhesus monkeys. No significant activity of TNF was seen against trophozoite-induced P. cynomolgi B infection. rHuIFN-(gamma) inhibited schizogony in functional human hepatocytes infected with P. falciparum sporozoites. These results suggest that the inhibitory effect of IFN is limited to the exoerythrocytic stage of parasite development. Interleukin-1 (IL-1) also inhibited hepatic development of P. falciparum sporozoites; however, IL-1 treatment was effective only when applied before sporozoite inoculation. IL-2 and TNF were effective in higher doses.