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Protective Effect of Interferon Inducers on Plasmodium Berghei Malaria^*

René I. Jahiel, Ruth S. Nussenzweig, Jan Vilek AND Jerome Vanderberg

We have studied the effect of three interferon inducers (Newcastle disease virus [NDV], statolon [S], and the complex of polyriboinosinic and polyribocytidylic acids [rI:rC]) on the course of malaria in mice inoculated with sporozoites or with erythrocytic forms of Plasmodium berghei. The number of parasitized cells per 10,000 erythrocytes was counted daily. Serum interferon was titrated in L-cell cultures. Parasitemia was prevented or its onset was delayed in mice treated with each inducer. Protection was greatest (survival and prevention of parasitemia) when NDV or S was given 16 to 24 hours after sporozoite inoculation. It was least (slight delay in onset of detectable parasitemia) when NDV or S was given before or after inoculation with erythrocytic forms. Mice were injected, 20 hours after inoculation of sporozoites, with diluted NDV or S, with heated S or with the supernatant of NDV-infected allantoic fluid after centrifugation at 100,000 x G. These procedures reduced both the serum-interferon-inducing and the protective effects of NDV or S. These results extend the spectrum of action of interferon inducers to a protozoon, P. berghei; they demonstrate a protective effect of interferon inducers against murine malaria; and they suggest that protection is mediated by interferons. They also show that sensitivity to the protective effect of interferon inducers varies during the development of P. berghei in the mouse.

^* This work, contribution No. 522 from the Army Research Program on Malaria, was carried out under the sponsorship of the Commission on Malaria, Armed Forces Epidemiological Board, and was supported in part by U. S. Army Medical Research and Development Command Contract No. DA-49-007-MD-964 and in part by U. S. Public Health Service grant AI07057.

Holder of U. S. Public Health Service Career Development Award IK4A138,784.

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