IL-10 DIFFERENTIALLY REGULATES MESSENGER-RNA EXPRESSION INDUCED BY LIPOPOLYSACCHARIDE AND INTERFERONS IN MURINE PERITONEAL-MACROPHAGES

IL-10 has been referred to as 'macrophage deactivator' because it supp resses macrophage activity by blocking cytokine production and accesso ry functions. The purpose of this study was to compare the effects of IL-10 on genes that are induced by the well characterized macrophage a ctivators, lipopolysaccharide (LPS) and interferons (IFNs). Using Nort hern blot analysis to measure the effects of IL-10 on the expression o f a large panel of LPS and IFN-inducible genes, the data suggest that in murine macrophages IL-10 is not a general suppressor of gene induct ion but, rather, exerts differential effects on gene expression. Induc tion of certain genes by LPS was indeed blocked to a great extent (70- 80%), while expression of others were less inhibited, not modulated at all, or augmented by IL-10. IFN-alpha and IFN-gamma induce a subset o f the genes that are also induced by LPS and, within this subset, IL-1 0 was found to interfere to a lesser extent with IFN- than LPS-induced gene expression. The participation of NF-kappa B in the induction of IL-10 inhibitable genes and shared common elements in IFN and IL-10 si gnaling pathways are discussed as potential explanations for these obs ervations.