Consistent with the multifactorial etiology of alcohol-associated liver disease, we identified strong combined effects of HPMA and proinflammatory cytokines (IL-1β, IL-8, and TNFα) on the extent/pattern of liver cell death, thereby supporting the pathogenic role of acrolein.
The use of probiotics with clinical evidence in liver disease, represent a novel therapeutic alternative, inducing positive changes in the balance of the intestinal microbiota which lead to improvement in liver function tests (AST and ALT), decreasing tumor necrosis factor-α (TNF-α), andblood cholesterol, among other risk factors.
Unsupervised analysis of multi-parametric data showed that liver disease was associated with the intrahepatic expansion of activated myeloid cells mainly composed of pro-inflammatory CD14<sup>+</sup>HLA-DR<sup>hi</sup>CD206<sup>+</sup> cells, which spontaneously produced TNFα and GM-CSF.
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) have been associated with liver disease.
In summary, Misoprostol was effective at beneficially modulating TNF and IL-10 levels both in vivo and in vitro; these studies suggest a potential rationale for Misoprostol use in ALD, NASH and other liver diseases where inflammation plays an etiologic role.
These results identify a new signaling pathway that regulates TNF-α production in LPS-induced liver damage and suggest potential cell-specific therapeutic targets for liver diseases in which TNF-α production is involved.
Importantly, Fn14 was the only TNF superfamily receptor exclusively upregulated in AH compared with other liver diseases and correlated with both 90-day mortality and severity of portal hypertension.
The efficacy of the inhibition of APE1 redox activity in blocking TNF-α and FAs induced inflammatory response opens new perspectives for treatment of inflammatory-based liver diseases.
The tumor necrosis factor receptor-associated factor family member-associated nuclear factor-κB (NF-κB) activator (TANK) takes part in the tumor necrosis factor-α (TNF-α)-mediated NF-κB signaling pathway and the interferon (IFN)-induction pathways that have relevance to HBV-related liver disease.
Compared with "alcoholic" controls without liver disease (n=110), TNFα -238AA genotype, IL1β -511CC genotype, TGFβ1 -509CC genotype and IL10 -592AA genotype were significantly overrepresented in ALD patients (n=181; OR=2.4 and 95% CI 1.2-5.5, P(genotype)=0.042, P(allelic)=0.008; OR=2.7 and 95% CI 1.2-5.9, P(genotype)=0.018, P(allelic)=0.023; OR=4.7 and 95% CI 1.7-13.1, P(genotype)=0.003, P(allelic)=0.014; and OR=2.2 and 95% CI 1.1-4.8, P(genotype)=0.04, P(allelic)=0.039 respectively).
The distribution of this polymorphism and its impact on the serum level of TNF-α was compared between 90 HCV-infected patients [45 with HCV-induced cirrhosis and 45 with HCV-related hepatocellular carcinoma (HCC)] and 45 healthy Egyptian volunteers without any history of liver disease.
Tumor necrosis factor (TNF) has been implicated in the progression of many chronic liver diseases leading to fibrosis; however, the role of TNF in fibrogenesis is controversial and the specific contribution of TNF receptors to hepatic stellate cell (HSC) activation remains to be established.
In this study, we tested the hypothesis that blocking TNF action with an anti-TNF monoclonal antibody (CNTO5048) will slow the progression of NPC liver disease.
TNF-alpha exerts its effects by binding to specific receptors (TNFR); the polymorphism of TNFRII T587G has been associated with increased TNF apoptotic response and its presence may increase the risk to develop liver disease.
These data identify an essential role for tnfa in the mutant phenotype and suggest a direct link between SAH-induced methylation defects and TNF expression in human liver disorders associated with elevated TNFalpha.
Inhibiting TNF-alpha expression in the liver by this strategy represents a novel therapeutic approach that may be valuable for the treatment of some inflammation-related liver diseases.
The study was aimed at investigating the level of serum TNF-alpha levels in adults and analyzing its relationship with different levels of alcohol consumption, as well as the potential interaction between alcohol consumption and common TNF-alpha gene polymorphisms in relation to TNF-alpha levels and liver disease.
No significant differences in the distribution of genotypes and alleles of the -308 TNFA gene polymorphism were observed between alcoholics and non-alcoholics, or between alcoholics with liver cirrhosis and those without liver disease.