Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

IL-10 is a potent anti-inflammatory cytokine and inhibitor of TNF-alpha production. The molecular pathways by which IL-10 inhibits TNF-alpha production are obscure, with diverse mechanisms having been published. In this study, a new approach has been taken for the study of human cells. Adenovirus was used to deliver TNF-alpha promoter-based luciferase reporter genes to primary human monocytic cells. The reporter genes were highly responsive to macrophage activation and appeared to mirror the behavior of the endogenous TNF-alpha gene. When added, either with or after the stimulus, IL-10 required the 3' untranslated region of the TNF-alpha gene to inhibit luciferase mRNA and protein expression, indicating a posttranscriptional mechanism. However, if macrophages were incubated with IL-10 before activation, inhibition of gene expression was also mediated by the 5' promoter, suggesting a transcriptional mechanism. To our knowledge, this is the first time that a dual mechanism for IL-10 function has been demonstrated. Studies to elucidate the mechanisms underlying the inhibition of TNF-alpha production addressed the effect of IL-10 on the activation of p38 mitogen-activated protein kinase and NF-kappaB. However, these studies could demonstrate no requirement for the inhibition of p38 mitogen-activated protein kinase or NF-kappaB activation as potential mechanisms. Overall, these results may explain the diversity previously ascribed to the complex mechanisms of IL-10 anti-inflammatory activity.

Original publication




Journal article


J immunol

Publication Date





4837 - 4845


3' Untranslated Regions, 5' Untranslated Regions, Adenoviridae, Cells, Cultured, Enzyme Activation, Enzyme Inhibitors, Gene Expression Regulation, Genes, Reporter, Humans, Immunosuppressive Agents, Interleukin-10, Lipopolysaccharides, Macrophages, Mitogen-Activated Protein Kinases, NF-kappa B, Promoter Regions, Genetic, RNA Stability, RNA, Messenger, Tumor Necrosis Factor-alpha, Zymosan, p38 Mitogen-Activated Protein Kinases