IL-4 and IL-10 inhibition of IFN-γ- and TNF-α-dependent nitric oxide production from bovine mononuclear phagocytes exposed to Babesia bovis merozoites

The requirement for IFN-γ and/or TNF-α as co-stimulants with Babesia bovis merozoites for nitric oxide (NO) production was examined, as well as the regulatory role of IL-4 and IL-10. Purified B. bovis merozoites did not induce the production of NO in undifferentiated monocytes without addition of exogenous IFN-γ and TNF-α unless the monocytes taken ex vivo were producing TNF-α endogenously. Under the latter condition, the NO production resulting from merozoite stimulation remained IFN-γ-dependent. There was no evidence for endogenous synthesis of TNF-α in monocyte-derived macrophages (MDM), and merozoites alone were incapable of inducing TNF-α mRNA in MDM. However, while merozoites plus IFN-γ induced TNF-α mRNA expression in MDM, NO was not produced. Both IL-4 and IL-10 inhibited expression of iNOS and production of NO in merozoite-stimulated monocytes.