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IL-10 has been referred to as 'macrophage deactivator' because it suppresses macrophage activity by blocking cytokine production and accessory functions. The purpose of this study was to compare the effects of IL-10 on genes that are induced by the well characterized macrophage activators, lipopolysaccharide (LPS) and interferons (IFNs). Using Northern blot analysis to measure the effects of IL-10 on the expression of a large panel of LPS and IFNinducible genes, the data suggest that in murine macrophages IL-10 is not a general suppressor of gene induction but, rather, exerts differential effects on gene expression. Induction 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-α and IFN-γ induce a subset of the genes that are also induced by LPS and, within this subset, IL-10 was found to interfere to a lesser extent with IFN- than LPS-induced gene expression. The participation of NF-KB in the induction of IL-10 inhibitable genes and shared common elements in IFN and IL-10 signaling pathways are discussed as potential explanations for these observations. [ABSTRACT FROM PUBLISHER]

IL-1 and its naturally occurring receptor antagonist, IL-1ra, are primarily synthesized by cells of the monocyte-macrophage lineage. The balance of the relative amounts of these secreted cytokines has major importance in the pathophysiology of various inflammatory disorders, especially bacterial sepsis and some autoimmune diseases. While both the agonist and the antagonist genes belong to the same family, IL-1β and IL-1ra are differentially regulated. In the present study, we examined the effects of macrophage activating factors, bacterial lipopolysaccharide (LPS), IFNα, and IFNγ, on the regulation of IL-1ra and IL-1β mRNA levels in thioglycollate-elicited mouse peritoneal macrophages. LPS-treatment of cultured macrophages resulted in a 3 to 4-fold increase in IL-1ra mRNA which peaked between 6-12 h, then started to decline but remained well above background levels at 24 h. In comparison to IL-1ra, the LPS-induced increase in IL-1β mRNA was larger, peaked earlier (at 2-4 h), and sharply decreased thereafter. In vivo analysis of mRNA from LPS-injected mice showed a similar temporal pattern of IL-1β and IL-1ra gene expression in bone marrow, spleen, and liver. In contrast to the effects of LPS, treatment with IFNα and IFNγ alone failed to affect the expression of either IL-1ra or IL-1β mRNA in vitro. However, in combination with LPS, IFNα and IFNγ had differential effects on the induction of these cytokines: IFNγ, but not IFNα, augmented the expression of LPS-induced IL-1ra. Conversely, both IFNα and IFNγ suppressed the induction of IL-1β mRNA by LPS. Thus, while IFNα only affects LPS-induced IL-1β gene expression, IFNγ exerts opposing effects on the LPS-induction of the agonist and antagonist, illustrating the complex role of interferons during the inflammatory process. [ABSTRACT FROM PUBLISHER]