Inhibition of the constitutive and induced IFN-beta production by IL-4 andIL-10 in murine peritoneal macrophages

We had previously reported that freshly harvested peritonea[ macrophages (P M) are in a type I IFN-mediated antiviral slate, which is lost during in vi tro culture of PM, concomitantly with a progressive decline in the expressi on of IFN-beta. We report herein that in vitro culture of PM in the presenc e of IL-4 or IL-10 results in an enhanced decay of the IFN-beta -mediated a ntiviral state to vesicular stomatitis virus (VSV). Moreover, IL-4 and IL-1 0 inhibited the production of type I IFN induced by LPS or NDV infection, a s assessed by IFN production and induction of IFN-mediated antiviral slate. The accumulation and physiological turnover of IFN-beta mRNA was not affec ted by IL-4 or IL-10. Finally, neither IL-10 nor IL-4 exerted any inhibitor y effect on the antiviral activity induced by exogenous type-I IFN. These r esults suggest that Th2 cytokines, such as IL-4 and IL-10, act as negative regulators of the type I IFN-mediated antiviral response in PM and may repr esent stop signals for the constitutive or induced type I IFN expression in PM. (C) 2000 Academic Press.