ANTIBABESIAL EFFECT OF THE IMMUNOMODULATOR AS101 IN MICE - ROLE OF INCREASED PRODUCTION OF NITRIC-OXIDE

The immunomodulator AS101 has been shown to induce cell proliferation and to increase the secretion of a variety of cytokines. In the presen t study we evaluated the effect of AS101 on the pathogenicity of B. ro dhaini infected mice. In order to clarify its mechanism of action we s tudied the ability of AS101 to activate neutrophils and macrophages, b oth of which inhibit parasite growth. More specifically, we studied th e ability of AS101 to induce secretion of nitric oxide (NO). We found that AS101 protects mice fi om babesiosis in a time and dose dependent manner. At 10 and 20 mu g/injection, two weeks prior to parasites, AS 101 significantly increased the number of neutrophils and mole than do ubled the survival rate of infected mice. Similarly, at these concentr ations when injected one month, or at 20 mu g, injected 24 h before pa rasites, AS101 mitigated the course of infection and reduced by half t he peak of parasitaemia. At 0.1 mu g/ml AS101 induced the secretion of significantly higher levels of NO in vitro than control. This was abr ogated by adding the NO synthase inhibitor, N-G-monomethyl-L-arginine. In vivo the antiparasitic protection of AS101 was abrogated by anothe r NO synthase inhibitor, aminoguanidine. We found that AS101, partly b y elevating levels of NO, can significantly mitigate the course of inf ection and thus increase survival, and may therefore be proven as an e ffective antiparasitic drug.