interleukin-8 and Hepatitis

Topics: Animals; Hepatitis; Humans; Interleukin-8; Ischemia; Liver; Neutrophils; Reperfusion Injury

Topics: Cell Adhesion; Chronic Disease; Cytokines; Hepatitis; Hepatitis, Alcoholic; Hepatitis, Viral, Human; Humans; Inflammation Mediators; Interleukin-1; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-5; Interleukin-6; Interleukin-8; Liver; Liver Cirrhosis; Tumor Necrosis Factor-alpha

Topics: Erythrocytes; Fatty Liver; Female; Hepatitis; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Receptors, Complement 3b; Thymosin; Tumor Necrosis Factor-alpha

Adenosine deaminase acting on RNA (ADAR) 1 binds and edits double-stranded (ds) RNA secondary structures found mainly within untranslated regions of many transcripts. In the current research, our aim was to study the role of ADAR1 in liver homeostasis. As previous studies show a conserved immunoregulatory function for ADAR1 in mammalians, we focused on its role in preventing chronic hepatic inflammation and the associated activation of hepatic stellate cells to produce extracellular matrix and promote fibrosis. We show that hepatocytes specific ADAR1 knock out (KO) mice display massive liver damage with multifocal inflammation and fibrogenesis. The bioinformatics analysis of the microarray gene-expression datasets of ADAR1 KO livers reveled a type-I interferons signature and an enrichment for immune response genes compared to control littermate livers. Furthermore, we found that in vitro silencing of ADAR1 expression in HepG2 cells leads to enhanced transcription of NFκB target genes, foremost of the pro-inflammatory cytokines IL6 and IL8. We also discovered immune cell-independent paracrine signaling among ADAR1-depleted HepG2 cells and hepatic stellate cells, leading to the activation of the latter cell type to adopt a profibrogenic phenotype. This paracrine communication dependent mainly on the production and secretion of the cytokine IL6 induced by ADAR1 silencing in hepatocytes. Thus, our findings shed a new light on the vital regulatory role of ADAR1 in hepatic immune homeostasis, chiefly its inhibitory function on the crosstalk between the NFκB and type-I interferons signaling cascades, restraining the development of liver inflammation and fibrosis.

Topics: Adenosine Deaminase; Animals; Extracellular Matrix; Gene Expression; Hep G2 Cells; Hepatic Stellate Cells; Hepatitis; Hepatocytes; Humans; Immunity, Innate; Interferon Type I; Interleukin-6; Interleukin-8; Liver; Liver Cirrhosis; Mice; Mice, Knockout; NF-kappa B; Paracrine Communication; RNA, Double-Stranded; Signal Transduction

An overdose of paracetamol is a frequent reason for liver and renal toxicity and possible death and curcumin has hepatoprotective properties against liver damage. The exact mechanism of such protection is not clear. Therefore, this study was conducted to examine the molecular levels of the protective effect of curcumin on paracetamol overdose induced hepatic toxicity in rats.. Male Wistar rats were allocated into 4 groups. Control group, administered corn oil; curcumin group, administered curcumin (400 mg/kg BW daily intra-gastric) dissolved in corn oil; paracetamol group, administered corn oil with a single dose of paracetamol (500 mg/kg BW intra-gastric) and protective group, administered curcumin with a single dose of paracetamol. Curcumin was administered for 7 successive days, while paracetamol was administered at day six of treatment. Blood and liver tissues were collected for biochemical, histopathological, immunohistochemical and molecular examination.. Serum analysis revealed an alteration in parameters of kidney and liver. A decrease in the antioxidant activity of liver was recorded in paracetamol group while curcumin administration restored it. Histopathological findings showed an extensive coagulative necrosis in hepatocytes together with massive neutrophilic and lymphocytic infiltration. Immunostaining of liver matrix metalloproteinase-8 (MMP-8) in paracetamol administered rats showed an increase in MMP-8 expression in the area of coagulative necrosis surrounding the central vein of hepatic lobules. Curcumin administration decreased MMP-8 expression in liver of paracetamol administered rats. Gene expression measurements revealed that paracetamol decreased the expression of antioxidant genes and increased the expression of interleukin-1β (IL-1β), IL-8, tumor necrosis factor-α (TNF-α) and acute phase proteins. Curcumin administration ameliorated paracetamol-induced alterations in genes expression of antioxidant and inflammatory cytokines.. The results clarified the strong protective effect of curcumin on paracetamol induced hepatic toxicity in rats at the immunohistochemical and molecular levels.

Topics: Acetaminophen; Acute-Phase Proteins; Analgesics, Non-Narcotic; Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Curcuma; Curcumin; Cytokines; Gene Expression; Hepatitis; Interleukin-1beta; Interleukin-8; Kidney; Liver; Male; Matrix Metalloproteinase 8; Necrosis; Neutrophil Infiltration; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Rats, Wistar; Tumor Necrosis Factor-alpha

Resistin is a cysteine-rich protein, which is abundantly expressed at the site of inflammation, and acts as a regulator of the NF-kB-dependent cytokine cascade. The aim of this study was to evaluate resistin levels in relation to inflammatory mediators, disease phenotype and autoantibody status in a spectrum of pathological conditions of the gastrointestinal tract. Resistin levels were measured with an ELISA in sera originated from 227 patients and 40 healthy controls (HC). Fifty patients diagnosed with non-alcoholic fatty liver disease (NAFLD), 53 ulcerative colitis (UC), 51 Crohn's disease (CD), 46 autoimmune hepatitis (AIH) and 27 primary sclerosing cholangitis (PSC) were included. The sera were analysed with respect to biochemical parameters of systemic inflammation and liver function and to the presence of antibodies to nuclear antigens (ANA), mitochondria (AMA) and smooth muscle (SMA). Compared with HC, resistin levels were raised in AIH (P = 0.017) and PSC (P = 0.03); compared with NAFLD, levels were elevated in CD (P = 0.041), AIH (P < 0.001) and PSC (P < 0.001). Patients with elevated levels of resistin were more often treated with corticosteroids, but no difference was found between active disease and clinical remission. Resistin levels were significantly higher in ANA-positive individuals compared with ANA-negative (P = 0.025). Resistin levels were directly correlated with IL-6 (r = 0.30, P = 0.02) and IL-8 (r = 0.51, P < 0.001). Elevated levels of resistin were prominent in patients with hepatobiliary inflammation and were associated with breach of self-tolerance, i.e. ANA positivity. Thus, we propose that resistin may be an important marker of disease severity in autoantibody-mediated gastrointestinal inflammatory diseases.

Topics: Adult; Aged; Antibodies, Antinuclear; Biomarkers; Cholangitis, Sclerosing; Disease Progression; Fatty Liver; Gene Expression Regulation; Hepatitis; Humans; Immune Tolerance; Inflammation Mediators; Inflammatory Bowel Diseases; Interleukin-6; Interleukin-8; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Resistin

Obese patients display an exaggerated morbidity during sepsis. Since consumption of a western-style diet (WD) is a major factor for obesity in the United States, the purpose of the present study was to examine the influence of chronic WD consumption on hepatic inflammation in mice made septic via cecal ligation and puncture (CLP). Feeding mice diets high in fat has been shown to enhance evidence of TLR signaling and this pathway also mediates the hepatic response to invading bacteria. Therefore, we hypothesized that the combined effects of sepsis and feeding WD on TRL-4 signaling would exacerbate hepatic inflammation. Male C57BL/6 mice were fed purified control diet (CD) or WD that was enriched in butter fat (34.4% of calories) for 3 weeks prior to CLP. Intravital microscopy was used to evaluate leukocyte adhesion in the hepatic microcirculation. To demonstrate the direct effect of saturated fatty acid on hepatocytes, C3A human hepatocytes were cultured in medium containing 100 μM palmitic acid (PA). Quantitative real-time PCR was used to assess mRNA expression of tumor necrosis factor-alpha (TNF-α, monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), toll-like receptor-4 (TLR-4) and interleukin-8 (IL-8).. Feeding WD increased firm adhesion of leukocytes in the sinusoids and terminal hepatic venules by 8-fold six hours after CLP; the increase in platelet adhesion was similar to the response observed with leukocytes. Adhesion was accompanied by enhanced expression of TNF-α, MCP-1 and ICAM-1. Messenger RNA expression of TLR-4 was also exacerbated in the WD+CLP group. Exposure of C3A cells to PA up-regulated IL-8 and TLR-4 expression. In addition, PA stimulated the static adhesion of U937 monocytes to C3A cells, a phenomenon blocked by inclusion of an anti-TLR-4/MD2 antibody in the culture medium.. These findings indicate a link between obesity-enhanced susceptibility to sepsis and consumption of a western-style diet.

Topics: Animals; Cecum; Chemokine CCL2; Diet; Disease Models, Animal; Fatty Acids; Hepatitis; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Ligation; Liver; Male; Mice; Mice, Inbred C57BL; Sepsis; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

The outcome of liver transplantation is steadily improving. Still there is need for earlier detection of complications like hepatic artery thrombosis and rejection. The aim of this study was to explore whether microdialysis with a 100-kDa cutoff filter could be used to monitor local inflammation after liver transplantation.. Twenty patients undergoing liver transplantations were observed for 1 week posttransplant. Microdialysis catheters were introduced in each liver lobe subcutaneously and metabolic parameters (glucose, pyruvate, glycerol, and lactate), cytokines (interleukin [IL]-6, IL-8, monocyte chemottractic protein-1, and inducible protein [IP]-10), and complement activation (C5a) were measured.. Fourteen patients experienced an uneventful course, judged clinically by ultrasound Doppler and by metabolic markers including lactate and the ischemia indicator lactate-to-pyruvate ratio. All patients with uneventful course had a consistent rise in IP-10 from 200 to 3000 pg/mL after transplantation, whereas the other cytokines stayed low. Two patients with rejection showed a selective increase in IL-8 and C5a, starting 2 to 4 days before alanine transferase increased, reaching 10- to 50-fold increase compared with baseline levels, and decreased rapidly after start of antirejection therapy. C5a concentration was substantially increased in these two patients at the time of transplantation. A third patient developed a hepatic artery thrombosis and rejection and showed a rapid rise in intrahepatic lactate and a complex inflammatory pattern.. Microdialysis using a 100-kDa filter is a promising way of monitoring the inflammatory reaction after liver transplantation. Increase in IP-10 reflects a normal pathophysiologic response posttransplant, whereas IL-8 and C5a were increased only in patients with rejection.

Topics: Adolescent; Adult; Aged; Biomarkers; Child; Child, Preschool; Complement Activation; Complement C5a; Cytokines; Female; Graft Rejection; Hepatitis; Humans; Infant; Interleukin-8; Liver; Liver Transplantation; Male; Membranes, Artificial; Microdialysis; Middle Aged; Molecular Weight; Monitoring, Physiologic; Thrombosis; Time Factors; Treatment Outcome

Extrahepatic cholestasis leads to complex injury and repair processes that result in bile infarct formation, neutrophil infiltration, cholangiocyte and hepatocyte proliferation, extracellular matrix remodeling, and fibrosis. To identify early molecular mechanisms of injury and repair after bile duct obstruction, microarray analysis was performed on liver tissue 24 hours after bile duct ligation (BDL) or sham surgery. The most upregulated gene identified encodes plasminogen activator inhibitor 1 (PAI-1, Serpine 1), a protease inhibitor that blocks urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) activity. Because PAI-1, uPA, and tPA influence growth factor and cytokine processing as well as extracellular matrix remodeling, we evaluated the role of PAI-1 in cholestatic liver injury by comparing the injury and repair processes in wild-type (WT) and PAI-1-deficient (PAI-1-/-) mice after BDL. PAI-1-/- mice had fewer and smaller bile infarcts, less neutrophil infiltration, and higher levels of cholangiocyte and hepatocyte proliferation than WT animals after BDL. Furthermore, PAI-1-/- mice had higher levels of tPA activation and mature hepatocyte growth factor (HGF) after BDL than WT mice, suggesting that PAI-1 effects on HGF activation critically influence cholestatic liver injury. This was further supported by elevated levels of c-Met and Akt phosphorylation in PAI-1-/- mice after BDL. In conclusion, PAI-1 deficiency reduces liver injury after BDL in mice. These data suggest that inhibiting PAI-1 might attenuate liver injury in cholestatic liver diseases.

Topics: Animals; Bile Ducts; Cell Proliferation; Cholestasis; Gene Expression Profiling; Hepatitis; Hepatocytes; Incidence; Infarction; Interleukin-8; Ligation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Plasminogen Activator Inhibitor 1; RNA, Messenger; Tissue Plasminogen Activator; Transcription, Genetic; Urokinase-Type Plasminogen Activator

To explore the relation between the pathogenesis and IL-8 level in the chronic hepatic disease and primary hepatocellular carcinoma.. 5ml venous blood was with drawn from 80 hospitaliged patients with different types of hepatic diseases and 14 healthy people. The serum was separated from the blood and then kept at -40 degrees Centigrade, and finally detected for IL-8 by ELISA.. There was an obvious difference among the IL-8 level in the serum from different types of hepatic disease patients. The IL-8 level was 75.80 microg/L 33.39 microg/L in chronic virus hepatitis and it was 89.54 microg/L 13.24 microg/L for primary hepatoma patients (t=10.48 and 4.01, respectively, P<0.01, as compared with control group).. There is a close relation between the level of IL-8 in serum and the state of illness. For patients with chronic hepatic diseases and primary hepatocellular carcinoma, the higher the IL-8 level is, the more serious the patients' condition, the worse the prognosis, and the higher the death rate would be.

Topics: Adult; Carcinoma, Hepatocellular; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis; Hepatitis, Viral, Human; Humans; Interleukin-8; Liver Diseases; Liver Neoplasms; Male; Middle Aged

To evaluate the possible roles of interleukin 18 (IL-18) in hepatitis B virus (HBV) infection.. Peripheral blood lymphocytes from 3 groups of HBV infectors (including 15 asymptomatic carriers, 30 patients with chronic hepatitis, 12 patients with fulminant hepatitis) and 10 blood donors (as normal controls) were analyzed. The transcription and expression of IL-18 in PBMC were assessed by semi-quantitive reverse transcription polymerase chain reaction and flow cytometry.. (1) There were significant differences in the transcription and expression levels of IL-18 between each group of HBV infectors. Interestingly, it was highest in fulminant hepatitis group, and lowest in asymptomatic carrier group. However there was no significant difference between chronic hepatitis and normal controls. The severity of disease was accompanied with the elevation of IL-18 production. (2) The severity degree of liver inflammation in chronic hepatitis was ccompanied with the elevation of IL-18 production. (3) The transcription and expression of IL-18 in chronic hepatitis B correlated with serum ALT positively (r = 0.54, P < 0.01; r = 0.63, P < 0.01). (4) There was a positive correlation in transcription and expression of IL-18 in each group of HBV infectors (asymptomatic carrier r = 0.980, P < 0.001; chronic hepatitis r = 0.910, P < 0.001; fulminant hepatitis r = 0.975, P < 0.001).. IL-18 may take part in the host immunity against HBV,and relate to the inflammation degree of liver.

Topics: Female; Gene Expression; Hepatitis; Hepatitis B; Hepatitis B virus; Humans; Immunity; Interleukin-8; Male; RNA, Messenger

Topics: Animals; Chemokine CXCL5; Chemokines; Chemokines, CXC; Chemotactic Factors; Disease Models, Animal; Growth Substances; Hepatitis; Integrins; Interleukin-8; Liver; Neutrophils; Tumor Necrosis Factor-alpha

Circulating levels of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in 13 children with autoimmune hepatitis (AIH) (seven with type 1 and six with type 2). In untreated children with type 1 AIH, TNF-alpha, IL-6, and IL-8 levels were elevated when compared to those of healthy controls (p < 0.005, p < 0.02, p = 0.06, respectively), whereas in children with type 2 AIH, cytokine levels were normal in all except one sample. A significant decrease in circulating IL-6, IL-8, and TNF-alpha was observed when patients were evaluated during a subsequent remission. We found no significant correlation of cytokine levels with alanine aminotransferase (ALT) activity, total serum gamma-globulins, or prothrombin activity. In patients with cirrhosis, serum IL-8 and IL-6 levels were higher (significantly in the case of IL-8) than those of patients without cirrhosis. In conclusion, activation of the in vivo production of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha appears to be associated with type 1 but not with type 2 AIH.

Topics: Adolescent; Alanine Transaminase; Autoimmune Diseases; Child; Child, Preschool; Hepatitis; Humans; Infant; Interleukin-6; Interleukin-8; Tumor Necrosis Factor-alpha

Acute alcoholic hepatitis is characterized by a unique degree of liver neutrophil infiltration, often accompanied by marked peripheral neutrophilia in the absence of demonstrable bacterial or fungal infection. In this study we assayed plasma and tissue levels of a potent neutrophil activator and chemotaxin, interleukin-8, in patients with a spectrum of alcoholic liver diseases and in normal and diseased control subjects. Levels of circulating interleukin-8 were undetectable in normal subjects but highly elevated in patients with alcoholic hepatitis, particularly in those who died (geometric mean = 600 ng/L; confidence interval = 323 to 1,120 vs. geometric mean = 184 ng/L; confidence interval = 114 to 309 in survivors). Levels correlated with biochemical indicators of severe disease (bilirubin: R = 0.38; international prothrombin ratio: R = 0.28; white blood cell count: R = 0.35; creatinine: R = 0.34) and with tumor necrosis factor-alpha (R = 0.43) and soluble tumor necrosis factor receptors (p55; R = 0.59). In contrast, moderate elevations in the levels of circulating interleukin-8 were seen in alcoholic cirrhosis (geometric mean = 93 ng/L; confidence interval = 40 to 213) and in alcoholic patients undergoing alcohol withdrawal (geometric mean = 137 ng/L; confidence interval = 72 to 259). Levels in nonalcoholic inflammatory liver disease were comparatively low (geometric mean = 17 ng/L; confidence interval = 10 to 29).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Autoimmune Diseases; Female; Hepatic Encephalopathy; Hepatitis; Hepatitis, Alcoholic; Humans; Immunohistochemistry; Interleukin-8; Liver; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Male; Neutrophils; Prospective Studies; Tumor Necrosis Factor-alpha