Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokine production in patients with hepatitis B may be related either to multiple immune abnormalities or to favourable outcome of the disease. Serum levels of IL-1 beta, IL-2, IL-6 and TNF-alpha were determined dynamically by ELISA kits in patients with self-limited form of acute hepatitis B infection (A-HBV) during the first, second and third decade after icterus appearance. IL-1 beta, IL-6 and TNF-alpha had characteristically high levels in patients measured in all decades, but these were the highest during the first. Then they gradually decreased, reaching normal values at the stage of convalescence. Serum IL-2 levels were found to be most significantly elevated during the second decade and also dropped to normal values in the course of the disease. Patients who cleared HBsAg on the third month after dehospitalisation had higher mean values of IL-2, IL-6 and TNF-alpha in comparison with those who were still HBsAg carriers, thus indicating that proinflammatory cytokine production in self-limited HBV may be important for viral clearance.
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PMID:Study on proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha) and IL-2 in patients with acute hepatitis B. 1046 29

The Th1/Th2 cytokine balance is important in persistence of infection and liver injury in chronic hepatitis C. The aim of this study was to administer the anti-inflammatory cytokine, recombinant human interleukin-10 (rHuIL-10), for 28 days in patients with chronic hepatitis C and to assess the safety and measure the effect on alanine aminotransferase (ALT, a marker of hepatic inflammation) levels and serum hepatitis C virus (HCV) RNA values. Three treatment-naive and 13 interferon (IFN) nonresponder patients (total 16 patients) with compensated chronic HCV infection were enrolled in this study. Patients were randomized to receive rHuIL-10 at a dose of 4 or 8 microg/kg/day as a single daily subcutaneous injection for 28 days. ALT values and serum HCV RNA were measured at days 0, 1, 3, 8, 15, 22, and 28 during therapy and at follow-up 2 and 4 weeks after cessation of the 4-week treatment period. ALT values normalized in 9 of 16 patients during therapy and remained normal until the end of treatment in 8 patients. The decreases in ALT values occurred in both the 4 microg and 8 microg dosage groups and were seen in both IFN naive and nonresponder patients. Mean ALT values fell significantly during the study period but usually returned to pretreatment levels by the end of the 4-week follow-up period (p < 0.05). HCV RNA concentrations did not vary significantly during or after therapy. (No patient had either an increase or a decrease in HCV RNA levels of > or =1.5 log during the study.) The drug was well tolerated, with no adverse symptoms noted. Platelet counts fell transiently to 73,000 and 63,000 in 2 patients. No other toxicity was observed, and no patients discontinued therapy. In chronic hepatitis C, short-term therapy with IL-10 was well tolerated and caused transient normalization of ALT values in 50% of patients, which returned to pretreatment levels on cessation of treatment. There were no significant changes observed in serum HCV RNA concentrations during the study. These immunomodulatory effects are similar to those observed with ribavirin monotherapy in chronic hepatitis C. Further study of rHuIL-10 alone or in combination with antiviral agents in chronic hepatitis C is warranted.
J Interferon Cytokine Res 1999 Nov
PMID:A pilot study of daily subcutaneous interleukin-10 in patients with chronic hepatitis C infection. 1057 19

Hypertrichosis of the eyelashes is a rare adverse effect of interferon-alpha treatment. We present a 21-year-old man with chronic renal failure and hepatitis B virus (HBV) infection who developed hypertrichosis of the eyelashes as a complication of IFN-alpha therapy. The patient was a candidate for living related renal transplantation and was given IFN-alpha 15 million units per week for HBV DNA positivity. After 6 months of therapy, HBV DNA positivity persisted, and the dose of IFN was increased to 30 million units per week. At the end of the first half of the second 6 months of therapy, the patient suffered from bilateral hypertrichosis of the eyelashes.
J Interferon Cytokine Res 2000 Jul
PMID:An unusual adverse effect of interferon: hypertrichosis of the eyelashes. 1092 5

This review describes a long-standing experience of screening for interferon (IFN) inducers in Russia. IFN inducers represent a special group of potential antiviral compounds. The main requirements for them are (1) high IFN-inducing activity, (2) absence of side effects, (3) wide spectrum of antimicrobial activity, (4) broad therapeutic security and, (5) good solubility in water and biologic liquids. IFN inducers stimulate IFN production in different cells and organs, and that determines the strategy for their application. Amixin (OOO "Lancepharm," Moscow, Russia) induces IFN-alpha/beta production mostly in T cells. Cycloferon (NTFF "Polysan," St. Petersburg, Russia) stimulates B cells and macrophages to produce almost pure IFN-alpha. Double-stranded RNA (dsRNA) and polyphenols of natural origin stimulate IFN production in different populations of immunocytes. Only polymers, such as Larifan (Riga, Latvia), Kagocel ("NIARnedicplus," Moscow, Russia), and Ragosin (N.F. Gamaleya Institute, Moscow, Russia), induce IFN synthesis in muscles, so they may be effective against rabies. Cycloferon, Larifan, and Kagocel, which induce IFN formation in lungs, may be effective against influenza and rhinoviral infections. Cycloferon and Larifan stimulate IFN production in liver and spleen and may be effective against hepatitis B. Oral compounds (Amixin, Kagocel) that stimulate IFN production in intestines may be effective against hepatitis A and enteroviral infections. Low molecular weight inducers (Amixin, Cycloferon, Kagocel) that penetrate the blood-brain barrier may be active against viral encephalitis. At present, clinical trials of IFN inducers are limited, but in the near future, IFN inducers may be used against very different infections and conditions.
J Interferon Cytokine Res 2001 Feb
PMID:Russian experience in screening, analysis, and clinical application of novel interferon inducers. 1124 70

Hepatitis B virus produces chronic infections of the liver leading to cirrhosis and hepatocellular carcinoma. The X protein of hepatitis B virus (HBx) is a multifunctional protein that can interact with p53 but can also influence a variety of signal transduction pathways within the cell. In most instances this small viral protein favors cell survival and probably initiates hepatocarcinogenesis. HBx upregulates the activity of a number of transcription factors including NF-kappa B, AP-1, CREB, and TBP. However, the majority of HBx is localized to the cytoplasm where it interacts with and stimulates protein kinases such as protein kinase C, Janus kinase/STAT, IKK, PI-3-K, stress-activated protein kinase/Jun N-terminal kinase, and protein kinase B/Akt. This small viral protein can localize to the mitochondrion. HBx may act as an adaptor or kinase activator to influence signal transduction pathways. This review will attempt to analyze the involvement of HBx in signal transduction pathways during hepatitis B viral infections and hepatocellular carcinoma development.
Cytokine Growth Factor Rev
PMID:X protein of hepatitis B virus modulates cytokine and growth factor related signal transduction pathways during the course of viral infections and hepatocarcinogenesis. 1132 2

Viral antigen-specific T cells are important for virus elimination. We studied the hepatitis B virus (HBV)-specific T cell response using flow cytometry. Three phases of HBV infection were studied: Group A, HBeAg (+) chronic hepatitis; Group B, HBeAb (+) HBV carrier after seroconversion; and Group C, HBsAb (+) phase. Peripheral T cells were incubated with recombinant HB core antigen (HBcAg), and intracytoplasmic cytokines were analysed by flow cytometry. HBcAg-specific CD4 and CD8 T cells were identified in all three groups and the number of IFN-gamma-positive T cells was greater than TNF-alpha-positive T cells. The frequency of IFN-gamma-positive CD4 and CD8 T cells was highest in Group C, compared with Groups A and B. No significant difference in the HBcAg-specific T cell response was observed between Group A and Group B. The HBcAg-specific CD8 T cell response was diminished by CD4 depletion, addition of antibody against human leucocyte antigen (HLA) class I, class II or CD40L. Cytokine-positive CD8 T cells without HBcAg stimulation were present at a high frequency (7 of 13 cases) in Group B, but were rare in other groups. HBcAg-specific T cells can be detected at high frequency by a sensitive flow cytometric analysis, and these cells are important for controlling HBV replication.
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PMID:High frequency of circulating HBcAg-specific CD8 T cells in hepatitis B infection: a flow cytometric analysis. 1147 5

The influence of 3-month interferon-alpha (IFN-alpha) treatment on plasma erythropoietin (EPO) concentration in patients with chronic active hepatitis (CAH) induced by hepatitis B virus (HBV) infection was investigated. The study was carried out in 44 nonanemic patients divided into two groups: CAH B, 30 subjects not treated with IFN-alpha, and CAH B-IFN, 14 subjects treated with IFN-alpha for the first 3 months of the study (5 MU/m(2) body surface subcutaneously (s.c.) three times per week). In all patients, blood samples were taken at the beginning of the study (0) and after 1, 2, 3, 6, 9, and 12 months of observation. At the beginning, plasma EPO levels in the CAH B (27.8 +/- 2.21 mU/ml) and CAH B-IFN (27.3 +/- 3.04 mU/ml) groups did not differ significantly from each other and were significantly higher (p < 0.0001) than in healthy subjects (10.4 +/- 1.06 mU/ml). In patients in the CAH B group, plasma EPO concentrations did not change significantly during the whole observation period. In patients in the CAH B-IFN group, a transient, significant increase in plasma EPO level was found. The highest plasma EPO concentration in this group was noted after the third month of treatment (41.1 +/- 3.41 mU/ml). In conclusion, patients with CAH induced by HBV infection are characterized by increased plasma EPO concentrations, and IFN-alpha treatment in these patients causes a transient increase in the plasma EPO level.
J Interferon Cytokine Res 2001 Sep
PMID:Influence of IFN-alpha on plasma erythropoietin levels in patients with hepatitis B virus-associated chronic active hepatitis. 1157 61

The signal transducer and activator of transcription 3 (STAT-3), a member of the STAT family of proteins, binds to a large number of transcriptional control elements and regulates gene expression in response to cytokines. While it binds to its cognate nucleotide sequences, it has been recently shown to directly interact with other transcriptional factors in the absence of DNA. We report here one such novel interaction between STAT-3 and hepatocyte nuclear factor 3 (HNF-3) in the absence of DNA. We have identified a STAT-3 binding site within the core domain of hepatitis B virus (HBV) enhancer 1. The HBV enhancer 1 DNA-STAT-3 protein interaction is shown to be stimulated by interleukin-6 (IL-6) and epidermal growth factor, which leads to an overall stimulation of HBV enhancer 1 function and viral gene expression. Using mobility shift assays and transient transfection schemes, we demonstrate a cooperative interaction between HNF-3 and STAT-3 in mediating the cytokine-mediated HBV enhancer function. Cytokine stimulation of HBV gene expression represents an important regulatory scheme of direct relevance to liver disease pathogenesis associated with HBV infection.
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PMID:Interaction between STAT-3 and HNF-3 leads to the activation of liver-specific hepatitis B virus enhancer 1 function. 1186 39

Cytokine dysregulation is an important factor underlying the immune unresponsiveness to hepatitis B vaccination (HBV) in renal transplant recipients. This study investigated the relationship between monocyte-derived interleukin-6 (IL-6) and interleukin-10 (IL-10) production and the immune responsiveness using flow cytometry (cytoflow) after whole blood culture. According to their previous response to hepatitis B vaccination, 40 renal transplant recipients were divided into two groups of 20 patients. The percentage of CD 14+ monocytes stained positive for intracellular IL-6 or IL-10 was measured using flow cytometry after 4 and 20 h of whole blood culture with lipopolysaccharide stimulation. The percentage of CD 14+/IL-6+ cells after incubation in vitro for 4 h was lower in the responders compared to the non-responders and controls (27.15+/-8.93 vs 35.47+/-9.95, P=NS; and 37.06+/-10.89, P<0.05 respectively). The staining intensity of IL-6 at 4 h for responders was also significantly reduced. At 20 h, there were a significantly higher percentage of CD 14+/IL-10+ positive cells in the responders compared to the non-responders (41.87+/-18.39 vs 27.55+/-17.25, P<0.05). These results indicate that alteration of intracellular cytokine profile in activated monocytes distinguishes the HBV vaccination responders from the non-responders among renal transplant recipients. The capacity to upregulate monocyte IL-10 production in this subset of patients may modulate the immune responsiveness and effectively assists in mounting a positive response to HBV vaccination.
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PMID:Significance of monocytic cytokines at single cell level for the immune responsiveness in renal transplant recipients. 1222 61

Recombinant interferon-alpha (rIFN-alpha) is currently used in the treatment of viral hepatitis either alone or in combination with small molecules. However, this treatment is not very efficacious, and more effective protocols are needed. To this end, we have explored the woodchuck hepatitis system, validated as an infection model for vaccination and antiviral studies against human hepatitis B virus (HBV) infection. The lack of a woodchuck IFN-alpha (WoIFN-alpha) homolog has prevented study of viral inhibition, which may be instrumental in understanding the IFN-alpha-induced antiviral pathways responsible for HBV clearance in humans. We have, therefore, cloned two WoIFN-alpha homologs from the woodchuck genome, which showed high similarity to the human IFN-alpha (HuIFN-alpha) gene at both nucleotide and amino acid levels. WoIFN-alpha showed a species-specific activity without any efficacy on human or mouse cells. In agreement with this antiviral activity, induction of Mx protein was observed in woodchuck cells only on WoIFN-alpha treatment. The antiviral efficacy of a WoIFN-alpha gene transfer was explored using a helper-dependent adenoviral (Ad) vector (HD-WoIFN) as a delivery vehicle. This treatment resulted in the reduction of woodchuck hepatitis viral proteins in primary hepatocytes from chronically woodchuck hepatitis virus (WHV)-infected woodchucks.
J Interferon Cytokine Res 2002 Oct
PMID:Expression of a new woodchuck IFN-alpha gene by a helper-dependent adenoviral vector in woodchuck hepatitis virus-infected primary hepatocytes. 1243 82


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