Interleukin 10 reduces lethality and hepatic injury induced by lipopolysaccharide in galactosamine-sensitized mice

Santucci, Luca; Fiorucci, Stefano; Chiorean, Michael; Brunori, PM; Matteo, FM Di; Sidoni, Angelo; Migliorati, Graziella; Morelli, Antonio

doi:10.1053/gast.1996.v111.pm8780580

Cited by 118 publications

(74 citation statements)

References 5 publications

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“…57 The mechanisms leading to decreased IL-10 and IL-4 production in rats exhibiting inflammatory liver injury is unknown but based on the biological activity of these anti-inflammatory cytokines, we hypothesize that decreased levels of IL-10 and IL-4 are important in determining the pathological outcome of liver injury. Thus, our results, taken in the context of protection experiments conducted with IL-4 and IL-10, 58,59 strengthen the idea that these cytokines are capable of antagonizing the production and effects of proinflammatory cytokines and, at least in rats fed saturated fats and ethanol, protect against the development of necroinflammatory changes. Our findings would predict a synergistic effect of IL-10 and IL-4 in protecting against the effect of proinflammatory cytokines.…”

Section: Figsupporting

confidence: 80%

Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat

et al. 1999

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Section: Figsupporting

confidence: 80%

Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat

et al. 1999

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“…The average of the score taken from 10 random fields was used to generate a single score for each animal's liver. Liver function was assessed by measuring plasma aspartate aminotransferase, bilirubin, albumin, ␥-glutamyl transpeptidase, and alkaline fosfatase levels by a 726 Hitachi (Tokyo) automatic analyzer as described (26).…”

Section: Liver Histology Collagen Immunohistochemistry and Biochemicalmentioning

confidence: 99%

NCX-1000, a NO-releasing derivative of ursodeoxycholic acid, selectively delivers NO to the liver and protects against development of portal hypertension

Fiorucci

Antonelli

Morelli

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

118

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Portal hypertension resulting from increased intrahepatic resistance is a common complication of chronic liver diseases and a leading cause of death in patients with liver cirrhosis, a scarring process of the liver that includes components of both increased fibrogenesis and wound contraction. A reduced production of nitric oxide (NO) resulting from an impaired enzymatic function of endothelial NO synthase and an increased contraction of hepatic stellate cells (HSCs) have been demonstrated to contribute to high intrahepatic resistance in the cirrhotic liver. 2-(Acetyloxy) benzoic acid 3-(nitrooxymethyl) phenyl ester (NCX-1000) is a chemical entity obtained by adding an NO-releasing moiety to ursodeoxycholic acid (UDCA), a compound that is selectively metabolized by hepatocytes. In this study we have examined the effect of NCX-1000 and UDCA on liver fibrosis and portal hypertension induced by i.p. injection of carbon tetrachloride in rats. Our results demonstrated that although both treatments reduced liver collagen deposition, NCX-1000, but not UDCA, prevented ascite formation and reduced intrahepatic resistance in carbon tetrachloride-treated rats as measured by assessing portal perfusion pressure. In contrast to UDCA, NCX-1000 inhibited HSC contraction and exerted a relaxing effect similar to the NO donor S-nitroso-N-acetylpenicillamine. HSCs were able to metabolize NCX-1000 and release nitrite/nitrate in cell supernatants. In aggregate these data indicate that NCX-1000, releasing NO into the liver microcirculation, may provide a novel therapy for the treatment of patients with portal hypertension

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“…IL-10 plays a protective role in low dose LPS-induced shock/ liver injury (46,47). After low dose LPS challenge, serum levels of IL-10 were significantly, although modestly, higher in LFA-1 Ϫ/Ϫ mice than in LFA-1 ϩ/Ϫ and C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 97%

“…Elevated serum levels of IL-10 in LFA-1 Ϫ/Ϫ mice following low dose LPS challenge IL-10 plays a protective role against both high dose (43-45) and low dose LPS-induced shock (46,47). To determine whether IL-10 participates in the increased resistance of LFA-1 Ϫ/Ϫ mice to low dose LPS-induced shock, serum levels of IL-10 were compared in LFA-1 Ϫ/Ϫ , LFA-1 ϩ/Ϫ , and C57BL/6 mice following challenge with LPS and D-GalN.…”

Section: Markedly Reduced Numbers Of Platelets In the Liver Of Lfa-1 mentioning

confidence: 99%

Increased Resistance of LFA-1-Deficient Mice to Lipopolysaccharide-Induced Shock/Liver Injury in the Presence of TNF-α and IL-12 Is Mediated by IL-10: A Novel Role for LFA-1 in the Regulation of the Proinflammatory and Anti-Inflammatory Cytokine Balance

Emoto¹,

Emoto²,

Brinkmann

et al. 2003

The Journal of Immunology

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Challenge with low doses of LPS together with d-galactosamine causes severe liver injury, resulting in lethal shock (low dose LPS-induced shock). We examined the role of LFA-1 in low dose LPS-induced shock. LFA-1−/− mice were more resistant to low dose LPS-induced shock/liver injury than their heterozygous littermates, although serum levels of TNF-α and IL-12 were higher in these mice. C57BL/6 mice were not rescued from lethal effects of LPS by depletion of NK1+ cells, granulocytes, or macrophages, and susceptibility of NKT cell-deficient mice was comparable to that of controls. High numbers of platelets were detected in the liver of LFA-1+/− mice after low dose LPS challenge, whereas liver accumulation of platelets was only marginal in LFA-1−/− mice. Following low dose LPS challenge, serum levels of IL-10 were higher in LFA-1−/− mice than in LFA-1+/− mice, and susceptibility to low dose LPS-induced shock as well as platelet accumulation in the liver of LFA-1−/− mice were markedly increased by IL-10 neutralization. Serum levels of IL-10 in LFA-1+/− mice were only marginally affected by macrophage depletion. However, in LFA-1−/− mice macrophage depletion markedly reduced serum levels of IL-10, and as a corollary, susceptibility of LFA-1−/− mice to low dose LPS-induced shock was markedly elevated despite the fact that TNF-α levels were also diminished. We conclude that LFA-1 participates in LPS-induced lethal shock/liver injury by regulating IL-10 secretion from macrophages and that IL-10 plays a decisive role in resistance to shock/liver injury. Our data point to a novel role of LFA-1 in control of the proinflammatory/anti-inflammatory cytokine network.

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Interleukin 10 reduces lethality and hepatic injury induced by lipopolysaccharide in galactosamine-sensitized mice

Cited by 118 publications

References 5 publications

Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat

Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat

NCX-1000, a NO-releasing derivative of ursodeoxycholic acid, selectively delivers NO to the liver and protects against development of portal hypertension

Increased Resistance of LFA-1-Deficient Mice to Lipopolysaccharide-Induced Shock/Liver Injury in the Presence of TNF-α and IL-12 Is Mediated by IL-10: A Novel Role for LFA-1 in the Regulation of the Proinflammatory and Anti-Inflammatory Cytokine Balance

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