Implication of inflammation‐related cytokines in the natural history of liver cirrhosis

Girón-González, José A; Martínez‐Sierra, Carmen; Rodríguez-Ramos, Claudio; Macías, Manuel; Rendón, Paloma; Díaz, Fernando; Fernández-Gutiérrez, C.; Martín‐Herrera, L.

doi:10.1111/j.1478-3231.2004.0951.x

Cited by 81 publications

(70 citation statements)

References 61 publications

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“…Putative signals implicated in the monocyte and lymphocyte activation are the following: (i) first, bacterial translocation and endotoxaemia are known causes of monocyte activation [12,14,43]. In fact, this was our original hypothesis.…”

Section: Cd25mentioning

confidence: 97%

“…In fact, this was our original hypothesis. Patients with increased LBP, a validated marker of endotoxaemia [11][12][13][14], present elevated serum levels of monocyte-derived cytokines or a higher percentage of regulatory T cells. It could be speculated that intestinal decontamination, for example with quinolones, could modify these altered factors.…”

Section: Cd25mentioning

confidence: 99%

“…LPS increases the plasma levels of LPS binding protein (LBP), the principal plasma protein responsible for transporting LPS to immune effector cells [11]. It has been proposed that high serum LBP identifies a subset of cirrhotic patients with ascites characterized by the immune cells being activated to produce tumour necrosis factor (TNF)-a and other proinflammatory cytokines [12][13][14][15]. Moreover, raised levels of circulating LBP or proinflammatory cytokines have been implicated in the endothelial activation and haemodynamic derangement observed in cirrhosis [12,16].…”

Section: Introductionmentioning

confidence: 99%

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Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis

Márquez¹,

Fernández-Gutiérrez²,

Montesdeoca³

et al. 2009

Clinical and Experimental Immunology

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SummaryThe objectives of this work were the analysis of the functional characteristics of circulating monocytes and T lymphocytes in patients with liver cirrhosis, and evaluation of the relationship with an increased exposure to antigens due to bacterial translocation. Forty patients with liver cirrhosis (20 with compensated cirrhosis and 20 with ascitic decompensation) and 20 healthy control subjects were studied. Bacterial translocation was evaluated by serum levels of lipopolysaccharide binding protein (LBP). Macrophage activation was studied by CD40 antigen expression. T lymphocytes were analysed for activation (CD25 + , CD122 + ), effector function (CD8 + CD45RO + CD57 + ), apoptosis (CD95 + ) and regulatory abilities, either by analysis of the membrane expression of co-stimulatory molecules CD80, CD86 and CD28, or by quantification of regulatory T cells CD4 + CD25 high forkhead box P3 (FoxP3). The percentage of activated monocytes and T lymphocytes in patients was increased significantly. The proportions of effector senescent cells and of those near to apoptosis were also significantly higher. With respect to these proportions, there were no significant differences between patients in function of the presence or absence of decompensation or in function of the increased or normal values of LBP. Conversely, those patients with elevated levels of LBP presented a significantly higher frequency of regulatory T cells than those with normal levels. In conclusion, patients with liver cirrhosis showed an intensive activation state with a higher percentage of cells committed to activation-induced death, even in non-advanced stages. It is possible that bacterial permeability and endotoxaemia contribute to the expansion of those lymphocyte populations implicated in the prevention of a more severe antigen-induced immunopathology.

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Section: Cd25mentioning

confidence: 97%

Section: Cd25mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis

Márquez¹,

Fernández-Gutiérrez²,

Montesdeoca³

et al. 2009

Clinical and Experimental Immunology

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“…Liver fibrosis is primarily due to a disproportion between the production and degradation of the extracellular matrix as a result of hepatocyte necrosis, mainly mediated by inflammation. Liver fibrosis is characterized by the release of cytokines, such as IL-6, IFN-γ, TGF-β1, platelet-derived growth factor (PDGF), TNF-α, insulin-like growth factor (IGF), hepatocyte growth factor (HGF), and IL-10 [16][17][18]. The relationship among specific immune response, viral clearance and inflammatory processes, is very complicated.…”

Section: Hepatitis C Virus and Cytokine Productionmentioning

confidence: 99%

“…Dendritic cells (DCs) present antigenic viral components to CD8 T and CD4 T cells. Th2 CD4 T cells induce B cells to produce antiviral antibodies, Th1 CD4 T cells secrete IFN-γ and induce the proliferation of cytotoxic CD8 cells, which represent a crucial element during viral infections through the destruction of infected cells and specific secretion of proinflammatory cytokines [16][17][18] (Figure 1).…”

Section: Hepatitis C Virus and Cytokine Productionmentioning

confidence: 99%

Rethinking cytokine function during hepatitis A and hepatitis C infections

Fierro¹,

Castro-García²,

Panduro³

2013

ABB

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Hepatitis A virus (HAV) and hepatitis C virus (HCV) are both viruses with hepatotropic lifestyles. HAV induces an acute infection that results in the elimination of the virus by the host whereas HCV is typically able to establish a persistent infection that may result in cirrhosis and hepatocellular carcinoma. The mechanisms responsible for this difference are unknown. However, given HAV and HCV are both non-cytophatic viruses, the observed symptoms and liver injury during the infections are the result of specific immune responses under the control of cytokines. Thus, the production of cytokines during hepatotropic viral infections may constitute a mechanism leading to different outcomes. Therefore, understanding the differences in the cytokine patterns induced in response to HAV and HCV is likely to provide important insights into the cytokine-mediated mechanisms underlying the long-term persistence of HCV, the broad spectrum of clinical manifestations induced by HAV and the resolution of HAV infection during the acute phase. Herein, we focus on discoveries that hold promise in identifying cytokines as therapeutic targets for the treatment of viral hepatitis.

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Ex vivo effects of high-density lipoprotein exposure on the lipopolysaccharide-induced inflammatory response in patients with severe cirrhosis

et al. 2008

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High-density lipoproteins (HDL) are known to neutralize lipopolysaccharide (LPS).Because patients with cirrhosis have lower HDL levels, this may contribute to LPS-induced ex vivo monocyte overproduction of proinflammatory cytokines. However, the effects of HDL on cytokine production by monocytes from patients with cirrhosis have never been studied. The aim of this study was to determine the effects of HDL on LPS-induced proinflammatory cytokine production in whole blood and isolated monocytes from patients with severe cirrhosis and controls. Plasma levels of HDL and cytokines were determined. The effects of reconstituted HDL (rHDL) on LPS-induced cytokine production in whole blood were assessed by cytokine array and on tumor necrosis factor alpha (TNF-␣) and interleukin-10 (IL-10) production in isolated monocytes. Plasma HDL levels were significantly lower in patients with cirrhosis than in controls. Plasma levels of TNF-␣ and IL-6 were significantly higher in patients with cirrhosis than in controls. Incubation of rHDL with whole blood prevented LPS-induced TNF-␣ and IL-6 overproduction in patients with cirrhosis. LPS-induced TNF-␣ production and CD14 expression were significantly more marked in cirrhotic monocytes than in control monocytes, and both decreased significantly after rHDL incubation. LPS-induced down-regulation of scavenger receptor, class B, type I (SR-BI) expression was abolished in cirrhotic monocytes. Conclusions: This study shows that rHDL abolishes the LPS-induced overproduction of proinflammatory cytokines in whole blood from patients with severe cirrhosis. These results were confirmed in isolated monocytes from these patients. This suggests that administration of rHDL might be a useful strategy for the treatment of cirrhosis to limit LPS-induced cytokine overproduction. (HEPATOLOGY 2009;49:175-184.)

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Implication of inflammation‐related cytokines in the natural history of liver cirrhosis

Abstract: In addition to the classic factors implicated in mortality (Child-Pugh score and hemodynamic parameters), alterations in inflammation-related components are of prognostic significance in cirrhotic patients.

Cited by 81 publications

References 61 publications

Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis

Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis

Rethinking cytokine function during hepatitis A and hepatitis C infections

Ex vivo effects of high-density lipoprotein exposure on the lipopolysaccharide-induced inflammatory response in patients with severe cirrhosis

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