UMLS:C0019158 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Circulating levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in children with autoimmune hepatitis. 788 14

To investigate the relationship between intrahepatic cytokine expression and interferon (IFN) response in chronic hepatitis C [CH(C)], interleukin (IL)-1 beta, -2, -4, -6, -8, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta mRNAs were investigated semiquantitatively by reverse transcription polymerase chain reaction using serial liver biopsies taken before and after IFN-alpha treatment from 24 patients with CH(C), including 12 responders and 12 non-responders. Before IFN treatment, IL-2, TNF-beta, IFN-gamma and IL-8 mRNA were associated with severe hepatitis activity whereas IL-4 mRNA was associated with weak hepatitis activity, regardless of IFN response. IL-2, TNF-beta and IFN-gamma mRNAs were significantly greater in IFN non-responders. After IFN treatment a complete response to IFN was significantly associated with the disappearance of these pro-inflammatory cytokines, whereas non-responders retained the expression of cytokine mRNA as before IFN treatment. Our results indicated that IFN-alpha treatment may modulate the intrahepatic cytokine network, and this may be one mechanism of IFN-alpha that reduces hepatitis activity, aside from an anti-viral effect. A difference in cytokine network may be involved in IFN response in CH(C).
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PMID:Intrahepatic expression of pro-inflammatory cytokine mRNAs and interferon efficacy in chronic hepatitis C. 902 19

The pathogenic mechanisms involved in viral hepatitis are not completely understood. Evidence suggests that the pathology associated with hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are a result of the immune response in the liver to these viruses. The livers of patients with viral hepatitis have been shown to contain elevated numbers of T cells expressing the gamma/delta form of the T-cell receptor for antigen (TCRgammadelta). In this study, we investigated whether liver biopsy specimens obtained from individuals with viral (HCV and/or HBV) or nonviral hepatitis contained TCRgammadelta(+) T cells that could be expanded in vitro by cytokines. A high percentage of liver biopsy specimens obtained from HCV- and/or HBV-infected individuals contained high numbers of TCRgammadelta(+) T cells. In contrast, T-cell lines generated from liver biopsy tissues obtained from individuals with nonviral hepatitis or from normal controls had no preferential expansion of TCRgammadelta(+) T cells. Liver TCRgammadelta(+) T-cell lines from HCV-infected individuals had high levels of non-major histocompatibility complex (MHC)-restricted cytotoxic activity against different targets including primary hepatocytes and produced interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin 8 (IL-8) following activation by anti-CD3. Surprisingly, none of these liver TCRgammadelta(+) T-cell lines could recognize any of the structural or nonstructural proteins of HCV and had no cytotoxic activity against cells infected with recombinant vaccinia viruses expressing different HCV proteins. However, the crosslinking of CD81, which has been shown to bind HCV particles and E2, resulted in significant levels of IFN-gamma and TNF-alpha production by liver TCRgammadelta(+) T cells. These results suggest that TCRgammadelta(+) T cells may play a role in the liver pathology of HCV infections.
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PMID:Characterization of liver T-cell receptor gammadelta T cells obtained from individuals chronically infected with hepatitis C virus (HCV): evidence for these T cells playing a role in the liver pathology associated with HCV infections. 1134 61

Immunotherapy with interferon-alpha (IFNalpha) may induce depressive symptoms, anxiety and major depression when administered for at least 1-3 months at a dose of 3-10 MUI daily, twice or three times a week. Previously, it has been shown that immunotherapy with interleukin-2 (IL-2) significantly induces the cytokine network, as measured by increases in serum IL-6, IL-10 and the IL-2 receptor (IL-2R), and that the immunotherapy-induced changes in the cytokine network are significantly correlated with the increases in depression ratings. The main aim of this study was to examine the effects of immunotherapy with IFNalpha on the cytokine network in relation to changes in depression and anxiety ratings. Fourteen patients, affected by chronic active C-hepatitis, were treated with IFNalpha (3-6 MUI s.c. three/six times a week for 6 months) and had measurements of serum IFN-gamma (IFNgamma), IL-2, IL-6, IL-6R, IL-8 and IL-10 before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFNalpha. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Repeated measure (RM) design ANOVAs showed significantly higher MADRS and HAM-A scores 2-4 weeks and 4-6 months after starting IFNalpha-based immunotherapy than at baseline. RM design ANOVAs showed significantly higher serum IL-6 and IL-8 levels 2-4 weeks after starting IFNalpha-based immunotherapy and higher serum IL-10 levels 2-4 weeks and 4-6 months after starting therapy than at baseline. There were significant relationships between the IFNalpha-induced changes in serum IL-6 or IL-8 and the depression and anxiety scores. The findings show that IFNalpha-based immunotherapy induces the cytokine network and that IFNalpha-induced increases in IL-6 predicts the development of depressive symptoms. Depressive symptoms following IFNalpha treatment may be secondary to cytokine induction, including that of IL-6.
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PMID:Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms. 1174 Sep 74

AIM:To assess the possible roles of cytokines (TNF-alpha, IFN-beta, IL-6 and IL-8) in liver damage of hepatitis B.METHODS:The serum TNF-alpha, IFN-beta, IL-6 and IL-8 were detected by ELISA in 66 patients with hepatitis B and 20 healthy blood donors.RESULTS:TNF-alpha and IL-6 in all types of clinical hepatitis B were significantly higher than those in healthy blood donors (P < 0.05); meanwhile the levels of TNF-alpha, IFN-beta, IL-6 and IL-8 in the patients with fulminant hepatitis B were much higher than those in the patients with acute hepatitis B (P < 0.05); the level of TNF-alpha was positively correlated with the levels of IFN-beta, Il-6 and IL-8 in all types of hepatitis B (r(IFN) = 0.24,r(IL6) = 0.35,r(IL8) = 0.44) and the TNF-alpha, IFN-beta, IL-6 and IL-8 were positively correlated with serum bilirubin (P < 0.05). Dynamic changes of these cytokines were observed in the course of acute and fulminant hepatitis. The level of IFN-beta peaked in the initial period of acute hepatitis and early stage of hepatic coma in fulminant hepatitis; TNF-alpha, IL-6 and IL-8 increased with exacerbation, and reached a peak when the liver damage was most serious, then decreased when patient conditions were improved.CONCLUSION:The increased cytokines were related to the inflammation of liver cells and multiple factors may play certain roles in liver damage.
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PMID:Detection of serum TNF-alpha,IFN-beta,IL-6 and IL-8 in patients with hepatitis B. 1181 82

Tumor necrosis factor alpha (TNF-alpha) not only induces apoptotic signals but also causes antiapoptotic and regenerative responses in the liver. However, the molecular mechanism(s) of the latter events remains unclear. In the present study, we examined TNF-alpha-induced genes in Hc human normal (unsensitized) hepatocytes by cDNA microarray analysis. Interleukin-8 (IL-8) induction was the most pronounced of the upregulated genes. The IL-8 protein level was also increased. IL-8 belongs to the ELR-CXC chemokine family and appears to exert mitogenic and antiapoptotic functions in other cell systems. IL-8 expression by TNF-alpha was inhibited when two survival signals, nuclear factor kappaB (NF-kappaB) and phosphatidylinositol 3-kinase (PI3K)/Akt, were inhibited by a mutant form of inhibitor of NF-kappaB (IkappaB); by dominant negative (kinase-dead) Akt; or by treatment with LY 294002, an inhibitor of PI3K. TNF-alpha induced apoptosis in Hc cells that were sensitized by inhibition of NF-kappaB and PI3K activation. IL-8 administration protected mice against concanavalin A-induced hepatitis in vivo. IL-8 also rescued the sensitized Hc cells, at least in part, from TNF-alpha-induced apoptosis in vitro. TNF-alpha inhibited DNA synthesis in unsensitized Hc cells in the absence of serum. Exogenous IL-8 reversed, though anti-IL-8 neutralization antibody enhanced, growth inhibition by TNF-alpha. These results indicate that IL-8, the production of which is stimulated by TNF-alpha, inhibits apoptosis of sensitized hepatocytes and releases normal (unsensitized) hepatocytes from growth inhibition induced by TNF-alpha.
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PMID:Tumor necrosis factor alpha-induced interleukin-8 production via NF-kappaB and phosphatidylinositol 3-kinase/Akt pathways inhibits cell apoptosis in human hepatocytes. 1237 8

An experimental model of the viral C-hepatitis (VCH) infection was worked out in vitro and it was found suitable to study the influence of interferon (IFN) preparations produced on the infection caused by an HCV cytopathogenic variations, i.e. the SW-13 human adrenocarcinoma cellular culture sensitive to the anti-VCH action of alpha-IFN and the MT-4 human lymphoblastoid cellular culture non-sensitive to the anti-VCH action of alpha-IFN. The above cellular models were employed to study, by using the methods of reverse transcription and polymerize chain reaction (RT-PCR), the influence produced by alpha-IFN on the VCH infectious activity as well as to study the changes in the activity of the below cytokine mRNAs: alpha-IFN, gamma-IFN, IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18 and TNF-alpha. A double treatment of the SW-13 alpha-IFN cellular cultures 24 and 48 hours after the infection was found to essentially suppress (by 4 Ig) reproduction of the VCH cytopathogenic variant. It was detected that the VCH reproduction is mediated by the regulation of a number of cytokine genes. The study results can be a basis for a more effective use of the alpha-IFN preparations in the therapy of VCH-infections.
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PMID:[Antiviral effect of alpha-interferon and cytokine mRNA level in cell cultures infected with a cytopathogenic variant of the hepatitis C virus]. 1260 58

Ethanol toxicity on liver is a function of duration of alcoholism, amount of daily intake of alcohol and patient's nutrition. The threshold of alcohol toxicity on the liver is about 40 g of ethanol daily in men and 20-30 g in women, however liver cirrhosis develops in no more than 8-20% of patients exceeding this values. Ethanol is oxidized in the liver to acetaldehyde--a compound considerably more toxic than ethanol itself. Despite small amount of alcohol dehydrogenase (ADH) found in gastric mucosa, the metabolism of ethanol in this site may have an important hepatoprotective effect. The oxidation of ethanol is associated with a change of hepatocyte redox homeostasis, which leads to a number of metabolic disorders such as lactic acidosis, hyperlipidaemia and hyperuricaemia. Chronic ethanol consumption does not influence ADH activity, but has a profound stimulatory effect on microsomal enzymes, in particular cytochrome CYP2E1. This fact is responsible for development in alcoholic liver associated with rise of oxygen consumption, excessive production of free radicals and increased metabolism of ethanol, vitamin A and testosterone. Ethanol and acetaldehyde have a deleterious effect, both the direct and indirect, on hepatocytes e.g., generating radical oxygen species and damaging intestinal mucosal barrier. Cellular oxidative stress that is caused by both an excess of free radicals and the antioxidatives' deficiency (glutathion, vitamin E, phosphatidylcholine), may be the principal factor responsible for progression of alcoholic liver disease. Among other factors accelerating alcohol-related liver lesion there are certain drugs, high fat diet, infection with HCV and genetic factors (female sex, enzymatic polymorphic forms of ADH and ALDH, hemochromatosis). Great importance in pathogenesis of necrotic and inflammatory hepatic events is being attributed to portal endotoxaemia and cytokines induced within the liver, in particular TNF-alpha and interleukin 8. These cytokines play a key role in development of alcoholic hepatitis, which clinical severity ranges from subclinical to fatal forms. Apart from abstinence, the treatment of alcohol liver disease is based on hyperalimentation, since alcoholism is generally associated with protein malnutrition. In severe forms of alcohol hepatitis corticosteroids are recommended.
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PMID:[Alcoholic liver disease]. 1290 Dec 71

Intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (HC-CC) are known to arise occasionally in hepatitis-related cirrhosis, although their clinicopathological features remain unclarified. In this study, we characterized the ICC (9 cases) and ICC elements of HC-CC (11 cases) arising in nonbiliary cirrhosis. Thirty-three hepatocellular carcinomas (HCC) associated with nonbiliary cirrhosis and 24 ICC without cirrhosis were used as controls. Prominent neutrophilic infiltration was frequent in ICC with cirrhosis (78%) and ICC elements of combined HC-CC (72%). Neutrophilic infiltration-related cytokines (interleukin 8, granulocyte colony-stimulating factor [G-CSF], and granulocyte macrophage colony-stimulating factor [GM-CSF]) were expressed frequently and intensely in carcinoma cells of ICC with cirrhosis (40%, 80%, and 60%, respectively) and in ICC elements of the combined one (13%, 38%, and 63%, respectively). Interleukin 8 was expressed in 18% of ICC without cirrhosis, irrespective of neutrophilic infiltration. Neutrophilic infiltration and expression of G-CSF and GM-CSF were in parallel (P < 0.05). G-CSF and GM-CSF mRNA were detected by RT-PCR in tissue specimens expressing G-CSF and GM-CSF at the protein level. Such neutrophilic infiltration and expression of G-CSF and GM-CSF were not evident in controls. The expressions of c-kit and c-Met, as a hematopoietic and hepatic stem cell marker, were seen frequently in ICC with cirrhosis (80% and 80%, respectively) and ICC elements of the combined one (63% and 50%, respectively). The present study revealed that the frequent expression of G-CSF and GM-CSF is a characteristic of ICC with cirrhosis and ICC in combined carcinoma, probably representing a phenotype of fetal hepatic parenchymal cell. The expression of these cytokines may be causally related to prominent neutrophilic infiltration.
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PMID:Intrahepatic cholangiocarcinoma in cirrhosis presents granulocyte and granulocyte-macrophage colony-stimulating factor. 1469 21

Glycyrrhizin (GL) is known to have various immunomodulating activities and has long been used clinically as an anti-allergic and anti-hepatitis agent. While the potency of GL against lung inflammatory diseases has been expected, the effect of GL on the lung has been poorly understood. Lung fibroblasts are known as a potent producer of inflammatory chemokines, IL-8 and eotaxin 1, by which neutrophils and eosinophils are strongly attracted during inflammation. Therefore, we studied the effects of GL on the production of these chemokines using a human fetal lung fibroblast cell line, HFL-1, stimulated with TNF-alpha and IL-4. Moreover, we examined the structure-activity relationships of GL to explore more beneficial compounds. 18alpha,beta-GL inhibited IL-8 dose-dependently and inhibited eotaxin 1 slightly. 18alpha,beta-Glycyrrhetic acid (GA) did not inhibit IL-8 but inhibited eotaxin 1. The effect of 18alpha,beta-glycyrrhetic acid monoglucuronide (MGA) resembled that of 18alpha,beta-GL but was weaker. Both 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-11-deoxo-olean-12-en-30-oic acid (11-deoxo-GL) and 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-olean-11,13,(18)-dien-30-oic acid (hetero-GL) exhibited inhibitory activity with significant cytotoxicity. 3beta-[(2-O-beta-D-Glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-olean-9,12-dien-30-oic acid (homo-GL) did not have cytotoxicity but its activity was mild like that of 18alpha,beta-GL. 3beta-[(2-O-beta-d-Glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol (hetero-30-OH-GL) and 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-olean-9,12-dien-30-ol (homo-30-OH-GL) showed potent inhibitory effects, at concentrations lower than 18alpha,beta-GL with no significant cytotoxicity. These results suggest that GL-related compounds are effective in reducing chemokine production and that GL-modified compounds including hetero-30-OH-GL and homo-30-OH-GL appear most beneficial in view of their inhibitory capacity with less cytotoxicity.
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PMID:Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line. 1545 16

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