interleukin-8 and Hepatic-Encephalopathy

The prognosis of acute liver failure (ALF) remains poor, and liver transplantation is an alternative treatment option. Assessing the prognosis of ALF is important in determining treatment strategies. Here, we investigated clinical factors including serum pro-inflammatory cytokine levels that are associated with the prognosis of ALF.. Sixty-six patients who developed ALF were enrolled in this study. Serum concentrations of 12 pro-inflammatory cytokines were measured on admission. The prognosis and factors associated with survival and development of hepatic coma were analyzed.. Of 66 patients, 4 patients underwent liver transplantation, and 49 patients were rescued without liver transplantation, while the remaining 13 patients died. Serum concentrations of interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-13, TNF, IFN -γ, IP-10, and G-CSF were significantly elevated in ALF patients. IL-4 and IL-8 levels were higher in patients who underwent liver transplantation or died than in rescued patients. Multivariable analysis identified age ≥ 55 years and IL-4 ≥ 1.2 pg/mL on admission as independent factors for mortality. Serum IL-8 levels were higher in patients with hepatic coma, and prothrombin-international normalized ratio ≥ 3.5 and IL-8 ≥ 77.2 pg/mL on admission were associated with development of hepatic coma after admission.. Serum levels of several pro-inflammatory cytokines were elevated in ALF patients. IL-4 and IL-8 were correlated with survival and development of hepatic coma after admission, respectively. Measurement of serum pro-inflammatory cytokines seems to be useful for the management of ALF.

Topics: Cytokines; Hepatic Encephalopathy; Humans; Interleukin-4; Interleukin-8; Liver Failure, Acute; Middle Aged; Prognosis

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that results from either acute or chronic liver failure. CXCR2 plays an essential role in the pathophysiology of liver and brain diseases. In the present study, the potential beneficial effects of SB332235, a selective inhibitor of CXCR2, against HE were evaluated.. HE was induced in male rats by thioacetamide injection (200 mg/kg, i.p.) at three alternative days. SB332235 was injected in rats 1 h before TAA at a dose of 1 and 3 mg/kg i.p.. SB332235 alleviated oxidative stress as shown by the decreased serum NO and reduced MDA, elevated GSH and SOD levels, and reduced TNF-α and NF-κB levels in both brain and liver tissues of rats. Additionally, SB332235 suppressed brain ASK-1, JNK, IL-8, and caspase-3 expression, and activated PI3K/AKT expression in brain tissues. Markers of brain dysfunction, such as ammonia, and markers of hepatic injury, such as LDH, albumin, bilirubin, γGT, AST, ALT, and ALP, were significantly ameliorated. Also, the protective effect of SB332235 was confirmed by histological examination of both brain and liver tissues.. Both doses (1 and 3 mg/kg) of SB332235 revealed significant hepatic/neuroprotective effects due to their anti-inflammatory, antioxidant, and antiapoptotic activities via activation of the PI3K/AKT pathway. Between the two, the 1 mg/kg dose provided significantly improved outcomes.

Topics: Albumins; Ammonia; Animals; Anti-Inflammatory Agents; Antioxidants; Bilirubin; Caspase 3; Hepatic Encephalopathy; Interleukin-8; Liver; Male; Neuroprotective Agents; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Superoxide Dismutase; Thioacetamide; Tumor Necrosis Factor-alpha

The influence of the immune system on the development of alcoholic liver disease has recently been the object of attention. However, the connection between alcohol consumption, altered immune response, and development of changes in the liver has not been fully explained. The aim of the present study was to evaluate serum IL-8 concentration in patients with chronic alcoholic liver disease.. 85 patients with different types of ALD and 35 healthy subjects were enrolled in the study. Serum IL-8 concentration was evaluated with the ELISA immunoenzymatic method. IL-8 in liver tissue was measured by the indirect immunofluorescence method.. There was a significant correlation between IL-8 concentration and AST, ALP, GGT, total bilirubin and albumin levels in blood serum. A significantly higher concentration of IL-8 was seen in all the groups of ALD patients. The highest values were found in patients with chronic alcoholic hepatitis, and the lowest in those with fatty liver. Significantly higher values were found in patients with ascites or encephalopathy in comparison to those without any features of portal hypertension and/or insufficiency of the liver cells. A high concentration of the tested cytokine is a disadvantageous prognostic factor in patients with ALD.. IL-8 appears to be an important factor in liver pathology in patients with ALD, especially in the development of the inflammatory process.

Topics: Ascites; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Fatty Liver, Alcoholic; Female; Fluorescent Antibody Technique, Indirect; Hepatic Encephalopathy; Hepatitis, Alcoholic; Humans; Interleukin-8; Liver; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Male; Prognosis

Neutrophil cytotoxity and activated macrophages have been implicated in the pathogenesis of alcohol-induced liver disease. The aim of this study was to relate plasma levels of neopterin, a marker of activation of the cellular immune system, and IL-8, a neutrophil chemotactic factor, with severity of liver disease and prognosis in patients with alcohol-induced cirrhosis.. Plasma concentrations of neopterin and IL-8 were assessed in 81 patients with alcohol-induced cirrhosis admitted to the Department of Medicine B, Bispebjerg Hospital, Copenhagen, Denmark, and in 16 healthy controls. After a median follow-up period of 5 years, mortality and death causes were registered. The patients were divided into groups according to the major contributing cause of death: infection, upper gastrointestinal bleeding or hepatic coma.. Neopterin and IL-8 levels were increased in the cirrhosis patients, but not significantly related to Child-Pugh classification. Five-year mortality was 67%. High neopterin levels (>upper quartile) were an independent predictor of death (p=0.01, Log rank and p<0.02, Cox). High IL-8 levels (>upper quartile) were of no significant prognostic value for overall mortality. Causes of death related mortality were as follows (Log rank): Neopterin; p=0.009, p=0.84 and p=0.94, and IL-8; p=0.36, p=0.002 and p=0.27, respectively, according to infection, bleeding and coma as causes of death.. Neopterin and IL-8 plasma levels are raised in patients with alcohol-induced cirrhosis, and are predictive of mortality associated with infections and upper gastrointestinal bleeding, respectively.

Topics: Cause of Death; Follow-Up Studies; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Interleukin-8; Liver Cirrhosis, Alcoholic; Neopterin; Pneumonia; Prognosis; Prospective Studies; Survival Analysis; Survival Rate

Patients with severe acute alcoholic hepatitis develop multiple organ failure which is associated with production of inflammatory cytokines and a poor prognosis. The aim of the present pilot study was to evaluate the effects of the BioLogic-DT sorption-suspension dialyser in patients with severe acute alcoholic hepatitis. Ten patients with encephalopathy (grade II-IV) were entered into the study, 5 received treatment with the BioLogic-DT for 6 hours daily for 3 days and 5 received conventional treatment as controls. The system was biocompatible with no adverse effects on blood pressure or platelet counts, factor V, fibrinogen or antithrombin III. No bleeding episodes were observed even with the use of small doses of heparin. After 3 days, blood ammonia was lower in the BioLogic-DT treated patients than in the controls, although blood lactate was higher. There were slight increases in plasma TNF and IL-8 during treatment over and above the higher levels present initially, possibly as a result of activation of white cells in the extracorporeal circuit. The further development of the BioLogic-DT dialyser with the addition of a plasma treatment module capable of removing cytokines would be worth evaluating in acute alcoholic hepatitis.

Topics: Acute Disease; Adult; Ammonia; Biocompatible Materials; Blood Coagulation; Cytokines; Female; Hepatic Encephalopathy; Hepatitis, Alcoholic; Humans; Interleukin-8; Lactic Acid; Liver, Artificial; Male; Middle Aged; Pilot Projects; 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