UMLS:C0019163 - FACTA Search

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Query: UMLS:C0019163 (hepatitis B)
38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor (TNF) plays a role in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The difference in the cytokine responses between hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may have implications in the pathogenesis of these diseases. We performed a comparative study to examine the possible differences in the TNF-TNF receptor (TNFR) response between CHB and CHC. We studied the cytokine levels of 38 patients with CHB, 40 patients with CHC and 9 patients with dual hepatitis B and C, and compared them with the baseline levels of 12 healthy controls. The plasma levels of TNF-alpha, interferon-gamma, interleukin (IL)-2, IL-4, IL-10 and soluble TNFR-1 and 2 (sTNFR-1 and 2) were quantified by enzyme-linked immunosorbent assays. The expression of TNFR-1 and 2 in liver tissues was examined in 30 cases of CHB and 15 cases of CHC by semiquantitative reverse transcription polymerase chain reaction. The results showed that sTNFR-1 levels correlated with liver inflammation in all patients, whereas this correlation was not found with sTNFR-2 or other cytokines. Liver inflammation indicators were higher in HCV RNA+ than in HCV RNA- CHC. Most significantly, sTNFR-1 levels correlated with liver inflammation in CHB, but not in CHC. However, the expression of TNFR-1 and 2 in liver was similar between CHB and CHC. These findings suggest that the TNFR signal transduction pathway is modulated differently in HBV and HCV infection.
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PMID:Modulation of tumor necrosis factor receptors 1 and 2 in chronic hepatitis B and C: the differences and implications in pathogenesis. 1145 94

Hepatitis B virus (HBV) core antigen (HBcAg) has extraordinary immunostimulatory properties. The majority of studies done so far on HBcAg induced responses have used ELISA or bioassay for cytokine determination and the 3[H]thymidine incorporation assay to measure proliferation. Here multiparameter flow cytometry was used to measure HBcAg induced cytokine production and proliferation of murine T cells. The advantage with this technique was that we could analyse the cytokine phenotype of proliferating cells of a particular cell type. We found that IL-10 expression was strongly induced in CD4+ T cells after HBcAg immunization. Importantly, we found that IL-4 producing HBcAg-specific CD4+ T cells are common after immunization although detection of IL-4 in culture supernatants indicates only low levels of IL-4. In contrast, IFN-gamma producing HBcAg-specific CD4+ T cells were found at lower numbers despite the detection of high levels of IFN-gamma in culture supernatants. Thus, the frequency of these cells is not accurately reflected by the detectability of the respective cytokine in culture supernatants. A low number of specific CD4+ T cells may effectively produce high levels of cytokine. We therefore suggest that different types of cytokine assays are used in order to obtain the most accurate picture of the intrinsic cytokine phenotype of the CD4+ T cells primed by HBcAg.
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PMID:Flow cytometric determination of cytokine production and proliferation in hepatitis B core antigen specific murine CD4 cells: lack of correlation between number of cytokine producing cells and cytokine levels in supernatant. 1168 33

Dendritic cell (DC)-dependent activation of liver NKT cells triggered by a single i.v. injection of a low dose (10-100 ng/mouse) of alpha-galactosyl ceramide (alphaGalCer) into mice induces liver injury. This response is particularly evident in HBs-tg B6 mice that express a transgene-encoded hepatitis B surface Ag in the liver. Liver injury following alphaGalCer injection is suppressed in mice depleted of NK cells, indicating that NK cells play a role in NK T cell-initiated liver injury. In vitro, liver NKT cells provide a CD80/86-dependent signal to alphaGalCer-pulsed liver DC to release IL-12 p70 that stimulates the IFN-gamma response of NKT and NK cells. Adoptive transfer of NKT cell-activated liver DC into the liver of nontreated, normal (immunocompetent), or immunodeficient (RAG(-/-) or HBs-tg/RAG(-/-)) hosts via the portal vein elicited IFN-gamma responses of liver NK cells in situ. IFN-beta down-regulates the pathogenic IL-12/IFN-gamma cytokine cascade triggered by NKT cell/DC/NK cell interactions in the liver. Pretreating liver DC in vitro with IFN-beta suppressed their IL-12 (but not IL-10) release in response to CD40 ligation or specific (alphaGalCer-dependent) interaction with liver NKT cells and down-regulated the IFN-gamma response of the specifically activated liver NKT cells. In vivo, IFN-beta attenuated the NKT cell-triggered induction of liver immunopathology. This study identifies interacting subsets of the hepatic innate immune system (and cytokines that up- and down-regulate these interactions) activated early in immune-mediated liver pathology.
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PMID:Activating immunity in the liver. II. IFN-beta attenuates NK cell-dependent liver injury triggered by liver NKT cell activation. 1193 27

Vaccination of healthy adults with recombinant hepatitis B (rHB) vaccine fails to induce a protective antibody response in a proportion of individuals. Imbalanced T-helper (Th)1/Th2 response has been attributed to the lack of specific antibody response to rHB vaccine. In this study, in vitro production of interleukin (IL)-2, interferon (IFN)-gamma and IL-10 was investigated in Iranian healthy adults vaccinated with rHB vaccine. Peripheral blood mononuclear cells (PBMC) were isolated from 18 high responders and eight nonresponders and stimulated with rHB antigen or phytohaemaglutinin (PHA) mitogen. The cytokines were quantitated in culture supernatants by sandwich enzyme-linked immunosorbent assay (ELISA). Our results demonstrated a significant decrease in the production of IL-2, IFN-gamma and IL-10 (P < 0.005) in response to rHB antigen. The levels of all cytokines induced by PHA were similarly represented in both groups of vaccinees. These findings suggest that unresponsiveness to rHB vaccine may be owing to inadequate Th1- and Th2-like cytokine production.
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PMID:Diminished Th1 and Th2 cytokine production in healthy adult nonresponders to recombinant hepatitis B vaccine. 1194 Feb 38

Matrix metalloproteases (MMPs) and their inhibitors are effector molecules involved in extracellular matrix remodelling. The serum profile for these proteolytic enzymes and their inhibitors during acute self-limiting viral hepatitis has not been studied. We therefore determined serum concentrations of MMP-1, MMP-3, MMP-2, MMP-9 and their inhibitors (tissue inhibitors of metalloproteinase) TIMP-1, TIMP-2 and alpha2 macroglobulin (AMG) in the serum of patients during the icteric stage of self-limiting acute viral hepatitis. Transforming growth factor-beta (TGF-beta) and interleukin (IL)-10, two cytokines involved in the regulation of MMPs and TIMPs were also assessed. Nineteen patients (12 men, seven women) with a mean age of 29.9 years (range 16-65 years) participated in the study. Fifteen had hepatitis B virus (HBV, two HCV and two HAV infection. The values of patients were compared with those obtained from 15 blood donor controls (eight men, seven women), mean age 36.2 years (range 18-55 years). Serum levels of TGF-beta, IL-10, MMP-1, MMP-3, MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed by ELISA. MMP-2 and MMP-9 were also measured by a zymogram protease assay. alpha2 macroglobulin (AMG) was measured by nephelometry. Compared with the healthy controls the mean serum concentrations of all MMPs were significantly decreased in the acute hepatitis patients. There was no difference in the serum concentration of TIMP-1 between patients and the controls. Serum levels of TIMP-2 (P < 0001), TGF-beta (P < 0.05), IL-10 (P < 0.001) and AMG (P < 0001) were increased in patients compared to healthy controls. A statistically significant negative correlation by linear regression analysis was found between AMG and MMP-1 (P=0003). The decreased levels of MMPs observed, together with normal and increased levels of TIMP-1 and TIMP-2, may indicate an attempt to limit matrix degradation at this stage of disease resolution. The increased levels of the anti-inflammatory cytokines IL-10 and TGF-beta might be the underlying mechanism responsible for the above effect. AMG inhibition especially for MMP-1 may play an additional important role.
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PMID:Matrix metalloproteinases and their inhibitors in acute viral hepatitis. 1201 May 6

Real-time polymerase chain reaction (PCR) assays were developed for woodchuck leukocyte cluster of differentiation (CD) and cytokine mRNA expression. Plasmid DNA standards of each marker (CD3, CD4, CD8, IL-2, IFN-gamma, TNF-alpha, IL-4, IL-10), and RNA standards from mitogen-stimulated woodchuck peripheral blood mononuclear cells (PBMCs) were used to validate and optimize the assays for TaqMan 7700 and iCycler PCR instruments. The complementary DNAs (cDNAs) produced by reverse transcription (RT) of RNA were quantified by real-time PCR against the plasmid DNA standards (6-8 log range) with detection of as few as 10-50 copies of amplicon cDNA per reaction. Analysis of unstimulated and concanavalin A-stimulated woodchuck PBMC demonstrated increased CD and cytokine mRNA expression following mitogenic activation. A liver sample from a woodchuck hepatitis virus (WHV) infected woodchuck with histologically confirmed acute hepatitis had increased intrahepatic CD and cytokine mRNAs compared to liver from an uninfected control woodchuck. The real-time PCR assays were highly specific for the woodchuck markers in PBMC and liver samples and were equally applicable for use in alternate real-time PCR instrumentation. These assays will enable the high-throughput analyses of mRNA markers during WHV infection, and thereby facilitate continued modelling of the immunopathogenesis and immunotherapy of human hepatitis B virus (HBV) infection.
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PMID:Real-time polymerase chain reaction assays for leukocyte CD and cytokine mRNAs of the Eastern woodchuck (Marmota monax). 1205 47

Chronic renal failure severely influences the immune functions of the host. Recent work has shown that uremic intoxication as well as its treatment alters distinct aspects of immunity and that the organism has certain mechanisms to compensate, at least in part, for these influences. Failure of the humoral branch of immune function becomes apparent when vaccinations are applied to the dialysis patient. Severely impaired vaccine responses are common, particularly against hepatitis B, tetanus, or influenza. In contrast, patients with chronic renal failure may develop adequate humoral responses against vaccines such as pneumococcus. The degree of impairment of humoral responses is related to the antigen's dependence on T-helper lymphocyte activation, which is high for hepatitis or influenza, and low for large polysaccharide antigens. T-helper cell activation on the other hand is greatly influenced by inflammatory processes, e.g. the secretion of cytokines such as interleukin (IL-)-1 or IL-6. These inflammatory processes are induced by uremic toxins and contacts between blood and extracorporeal surfaces of the dialysis equipment. They are subject to the body's compensatory mechanisms for inflammation, which are mainly based on the anti- inflammatory cytokine IL-10. Genetically determined differences in the secretion capacity for this compensatory cytokine strongly influence humoral immunity in the patient with chronic renal failure and thus allow the definition of a high-risk group for infection and vaccine nonresponse.
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PMID:Humoral immune responses in uremia and the role of IL-10. 1220 99

Yeast expressed Hepatitis B surface antigen (rHBsAg) binds to monocytes through interaction with the LPS binding protein (LBP) and the LPS receptor CD14. Charged phospholipids of rHBsAg determine the interaction with these proteins. Although attachment of rHBsAg resembles the pro-inflammatory binding of LPS to CD14, rHBsAg does not activate monocytes and even reduces the expression of pro-inflammatory cytokines by LPS-stimulated monocytes. It is reported here that addition of rHBsAg to LPS-stimulated PBMC often results in increased secretion of IL-10, suggesting a similarity between the interaction of monocytes with apoptotic cells and rHBsAg. Using THP-1 cells, it is shown that IL-10 is not necessary to reduce TNFalpha protein levels. Addition of rHBsAg to LPS-stimulated cells reduces TNFalpha mRNA levels, but does not affect phosphorylation of p65 NF-kappaB and p38 MAP kinase. Instead, a reduced phosphorylation of ERK-1/2 and JNK-1/2 MAP kinases is observed.
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PMID:Recombinant HBsAg, an apoptotic-like lipoprotein, interferes with the LPS-induced activation of ERK-1/2 and JNK-1/2 in monocytes. 1227 Jan 19

In murine models, overexpression of interleukin (IL)-12 and interferon (IFN)-gamma can induce severe liver damage, whereas IL-10 has anti-inflammatory and hepatoprotective properties. To analyze the potential role of these cytokines in human fulminant hepatitis B, we used immunohistochemistry to study expression of IL-12, IFN-gamma, and IL-10 in explant livers of 11 patients with fulminant hepatitis B, 5 patients with fulminant hepatitis due to other etiologies, 37 patients with chronic liver disease (CLD; hepatitis B virus, n = 15; hepatitis C virus, n = 10; primary biliary cirrhosis, n = 12), and 10 normal controls (NCs). Furthermore, cytokine messenger RNA (mRNA) levels were determined in the liver specimens by quantitative real-time polymerase chain reaction (PCR). In NCs, faint IL-12 expression was detected in only a few Kupffer cells, whereas sinusoidal endothelial cells, hepatic stellate cells, bile ducts, and lymphocytes expressed IL-12 in CLD and, more conspicuously, in fulminant hepatitis B. In contrast, expression of IFN-gamma and IL-10 was restricted to lymphocytes and Kupffer cells, respectively. In fulminant hepatitis B, numbers of IL-12- and IFN-gamma-positive cells markedly exceeded those found in CLD and NCs. A close correlation existed between IL-12 and IFN-gamma expression (r = 0.68; P <.001). In contrast, IL-10 expression was not significantly different in CLD and fulminant hepatitis. The quantitative differences in immunohistologic cytokine expression closely corresponded to the mRNA levels. In conclusion, our data indicate massive induction of the proinflammatory cytokines IL-12 and IFN-gamma in fulminant hepatitis B, which is apparently not counterbalanced by the anti-inflammatory cytokine IL-10. This cytokine imbalance may play an important role in promoting inflammatory reactions leading to massive liver damage in fulminant hepatitis B.
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PMID:Imbalanced intrahepatic expression of interleukin 12, interferon gamma, and interleukin 10 in fulminant hepatitis B. 1229 50

The immunoregulatory roles of interleukin-2 (IL-2), IL-4, IL-10, gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), the soluble form of the IL-2 receptor (sIL-2R), and the soluble form of CD30 (sCD30) were evaluated in patients with hepatitis B virus (HBV) infection. Two groups of subjects were studied: 15 healthy individuals without hepatitis antecedents and 15 patients with HBV infection. Blood samples were taken during the acute and convalescent phases. The analysis of the samples was done by the enzyme-linked immunosorbent assay technique. IFN-gamma and TNF-alpha levels decreased in the convalescent phase. IL-10, IL-2, and sIL-2R levels increased in the acute and convalescent phases, while sCD30 levels increased during the acute phase. The IL-4 concentrations decreased in both phases. During the acute phase, IFN-gamma and TNF-alpha induced increases in IL-2, sIL-2R, IL-10, and sCD30 levels in serum, which allowed the development of immunity characterized by the nonreactivity of the HBV surface antigen, the onset of antibodies to the HBV surface antigen (anti-HBs), and normal alanine aminotransferase levels during the convalescent phase. Increased IL-2 levels during the acute phase would stimulate the activities of NK cells and CD8(+) lymphocytes, which are responsible for viral clearing. The raised sIL-2R levels reveal activation of T lymphocytes and control of the IL-2-dependent immune response. The sCD30 increment during the acute phase reflects the greater activation of the Th2 cellular phenotype. Its decrease in the convalescent phase points out the decrease in the level of HBV replication. The increase in IL-10 levels could result in a decrease in IL-4 levels and modulate IFN-gamma and TNF-alpha levels during both phases of disease, allowing the maintenance of anti-HBs concentrations.
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PMID:Concentrations of cytokines, soluble interleukin-2 receptor, and soluble CD30 in sera of patients with hepatitis B virus infection during acute and convalescent phases. 1241 77

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