Endogenous Interleukin-10 Protects against Hepatic Steatosis but Does Not Improve Insulin Sensitivity during High-Fat Feeding in Mice

Boer, Marion A. M. den; Voshol, Peter J.; Elst, J.P. Schröder-van der; Korsheninnikova, Elena; Ouwens, D. Margriet; Kuipers, Folkert; Havekes, Louis M.; Romijn, Johannes A.

doi:10.1210/en.2006-0417

Cited by 72 publications

(53 citation statements)

References 34 publications

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“…In agreement with the well-known immunomodulatory activity of IL-10 in several tissues, several studies have reported a role for IL-10 as a protective cytokine against hepatic injury in diseases such as diet-induced insulin resistance in liver (Cintra et al, 2008), experimental hepatitis induced by LPS (Santucci et al, 1996) and concanavalin A (Louis et al, 1997), schistosomiasis (Winn et al, 1998), alcoholic hepatitis (Le Moine et al, 1995), hepatitis C virus infection (Kaplan et al, 2008) and fatty liver disease (Den Boer et al, 2006). The immunosuppressive cytokine IL-10 is crucial for tolerance induction in concanavalin A-induced liver damage in mice and is mainly expressed by CD4 + CD25 + regulatory T cells (Erhardt et al, 2007).…”

Section: The Antiinflammatory Cytokine Il-10 Is Regulated By Nf-kb1 (mentioning

confidence: 53%

NF‐κB in liver diseases: a target for drug therapy

Muriel

2008

J of Applied Toxicology

147

106

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There are five nuclear factor-kB (NF-kB) transcription factors with important roles in innate immunity, liver inflammation, fibrosis and apoptosis prevention. Several inhibitors of NF-kB, like caffeic acid, captopril, curcumin, pyrrolidine dithiocarbamate, resveratrol, silymarin and thalidomide, have demonstrated antinecrotic, anticholestatic, antifibrotic and anticancer activities in the liver. A link between inflammation and hepatocellular carcinoma through the NF-kB pathway has been observed, providing ample experimental support for the tumor-promoting function of NF-kB in various models of cancer. NF-kB has been associated with the induction of proinflammatory gene expression and has attracted interest as a target for the treatment of inflammatory disease. However, despite much attention being focused on the deleterious effects of NF-kB, activation of this factor during the resolution of inflammation is associated with the production of antiinflammatory molecules like interleukin (IL)-10 and the onset of apoptosis. This suggests that NF-kB has an antiinflammatory role in vivo involving the regulation of the resolution of inflammation. Also, NF-kB promotes liver regeneration by upregulating IL-6 and other molecules like hepatocyte growth factor. It has been postulated that the beneficial properties of NF-kB are due to p50 homodimers, whose activation prevents cholestatic and chronic liver injury. More basic understanding on the function of the diverse NF-kB factors is urgently needed in different physiological and pathological conditions, because depending on the subunit composition of the dimmer, the disease and the stage of the illness, inhibition of the factor may result in a beneficial or in a deleterious response. Copyright © 2008 John Wiley & Sons, Ltd.There are five nuclear factor-kB (NF-kB) transcription factors with important roles in innate immunity, liver inflammation, fibrosis, and apoptosis prevention. Several inhibitors of NF-kB have demonstrated antinecrotic, anticholestatic, antifibrotic and anticancer activities in the

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Section: The Antiinflammatory Cytokine Il-10 Is Regulated By Nf-kb1 (mentioning

confidence: 53%

NF‐κB in liver diseases: a target for drug therapy

Muriel

2008

J of Applied Toxicology

147

106

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“…Furthermore, infliximab treatment effectively inhibited the expression of the proinflammatory cytokines, IL-6, and IL-1b, while the antiinflammatory cytokine IL-10 was not affected by the treatment. The maintenance of higher levels of IL-10 may have a positive impact on the overall result of the treatment, as suggested by recent studies that show a protective effect of this cytokine in NASH development (den Boer et al 2006, Elinav et al 2006. Another outcome of the treatment with infliximab was the reduction of SOCS-3 expression.…”

Section: Discussionmentioning

confidence: 92%

Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet

Barbuio

Milanski

Bértolo

et al. 2007

Journal of Endocrinology

137

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Non-alcoholic fatty liver disease, induced by nutritional factors, is one of the leading causes of hepatic dysfunction in the modern world. The activation of proinflammatory signaling in the liver, which is induced by systemic and locally produced cytokines, and the development of hepatic insulin resistance are two important factors associated with the progression from steatosis to steatohepatitis, a pre-cirrhotic condition. The objective of the present study was to evaluate the effect of inhibition of tumour necrosis factor (TNF)-a, using the monoclonal antibody infliximab, on the expression of cytokines, induction of steatosis and fibrosis, and insulin signal transduction in the liver of Wistar rats fed a high-fat diet. Ten days of treatment with infliximab significantly reduced the expression of the proinflammatory markers, TNF-a, IL-6, IL-1b, and SOCS-3, in the liver of rats fed a high-fat diet. This was accompanied by reduced fat deposition and fibrosis and by improved insulin signal transduction through insulin receptor (IR)/IR substrate/Akt/FOXO1 and JAK2/STAT3 pathways. In conclusion, short-term inhibition of TNF-a with infliximab reduces inflammation and steatosis/fibrosis, while improving insulin signal transduction in an animal model treated with a high-fat diet.

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“…Interleukin 10 (IL10) is a cytokine with pleiotropic effects on immunoregulation and inflammation. It has been shown to improve insulin resistance and reduce hepatic steatosis [60] . The insulinlike growth factor binding protein 3 (IGFBP3) is one of six high-affinity binding proteins for IGFs that reduce the levels of free IGF and antagonize their insulin-like activity.…”

Section: Discussionmentioning

confidence: 99%