Interleukin-10 suppresses IP-10 gene transcription by inhibiting the production of class I interferon

Interleukin-10 (IL-10) selectively inhibited lipopolysaccharide (LPS)-induc ed chemoattractant cytokine gene expression: levels of IP-10 mRNA were mark edly suppressed in IL-10-treated mouse peritoneal macrophages, whereas the expression of the RANTES mRNA was only modestly reduced, IL-10 inhibited IP -10 mRNA accumulation by reducing IP-10 gene transcription as demonstrated by nuclear run-on analysis, Interestingly, the ability of IL-10 to inhibit expression of IP-10 was dependent on the inducing stimulus; IL-10 did not s uppress interferon gamma (IFN gamma)- or IFN beta-stimulated IP-10 transcri ption or mRNA accumulation. These results suggested that IL-10 might act in directly to suppress IP-10 expression by inhibiting LPS-induced class I IFN production. This hypothesis was supported by the following observations. F irst, LPS-induced IP-10 mRNA expression was blocked in cells cotreated with cycloheximide, Second, IL-10 inhibited the production of IFN alpha/beta-me diated antiviral activity. Finally, the IL-10-mediated suppression of LPS-s timulated IP-10 production could be rescued by cotreatment with IFN beta. ( C) 1998 by The American Society of Hematology.