Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We obtained peripheral blood mononuclear cells from 12 chronic hepatitis Type B patients, 12 Type C patients, and 15 healthy volunteers, and investigated the effects of OK-432, a streptococcal preparation, on in vitro production of 3 types of cytokines. Mononuclear cells in a concentration of 1 x 10(6) cell/ml were prepared in the culture medium. OK-432 (Chugai Pharmaceutical Co., Ltd., Tokyo) was added to this preparation and incubated for one to 4 days. Thereafter interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) levels in the culture supernatant were measured using enzyme-linked immunoassay kits. Cytokine production levels in cultures with OK-432 were significantly increased in the mononuclear cells of both patients and healthy volunteers. The largest increase was observed with IFN-gamma (p < 0.01), and then with IL-1 beta (p < 0.05). Responses of the cells from chronic hepatitis Type C patients to OK-432 were relatively good. When interferon (alpha and beta) treatment was first introduced, there were high hopes for a high efficacy. However, we now know 50-70% of patients with chronic hepatitis Type C do not respond satisfactorily to interferon. Some physicians suggest the necessity of using biological response modifier (BRM) as an adjuvant treatment for these patients. From our findings, OK-432 could be a useful BRM in patients with chronic hepatitis Type C.
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PMID:Effects of the streptococcal preparation OK-432 on in vitro cytokine production of peripheral blood mononuclear cells in patients with chronic viral hepatitis. 134 50

A 49-yr-old man with chronic hepatitis B manifested hypergammaglobulinemia, lymphadenopathy, and a high serum interleukin-6 level following treatment with recombinant human alpha-interferon. One month later, when the patient was treated with natural beta-interferon, serum levels of interleukin-6 and gamma-globulin increased again. The serum gamma-globulin decreased to the pretreatment level after discontinuation of interferon therapy. The serum alanine aminotransferase level remained normal for 6 months. In this case, hypergammaglobulinemia and lymphadenopathy, as well as the elevated serum interleukin-6 level, were considered to be signs of highly enhanced humoral immunity related to alpha- and beta-interferon therapy.
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PMID:Elevated interleukin-6 and gamma-globulin during interferon therapy of hepatitis B. 138 10

The in vitro production of the acute-phase mediator interleukin-6 by peripheral blood monocytes derived from patients with various liver diseases was studied. Compared with healthy controls (n = 45; 860 +/- 92 U/ml, mean +/- SEM), monocytes from patients with chronic hepatitis B produced significantly lower amounts of interleukin-6 (n = 14; 424 +/- 126 U/ml) after stimulation with lipopolysaccharide (p = 0.02), whereas monocytes from patients with chronic hepatitis non-A, non-B secreted normal amounts of interleukin-6 (n = 13; 672 +/- 151 U/ml; n.s.). In contrast, monocytes of patients suffering from alcoholic liver cirrhosis (n = 22; 1310 +/- 153 U/ml) or primary biliary cirrhosis (n = 6; 1450 +/- 186 U/ml) produced higher amounts of interleukin-6 than healthy control individuals (p = 0.03, respectively). Lipopolysaccharide-stimulated monocytes derived from patients with acute hepatitis A, B and non-A, non-B showed an interleukin-6 production not different from that seen in healthy control individuals and did not experience a discernible change during the course of the acute disease. These results suggest that the production of the acute-phase mediator interleukin-6 varies in chronic liver disease in accordance with various etiologies with a reduced lipopolysaccharide-inducible interleukin-6 response in chronic hepatitis B and an enhanced response in alcoholic liver cirrhosis and primary biliary cirrhosis.
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PMID:Interleukin-6 production by peripheral blood monocytes in patients with chronic liver disease and acute viral hepatitis. 144 5

It is well known that several inflammatory cytokines can modulate hepatocellular gene expression in a complex physiological process known as the hepatic acute-phase response. Since hepatitis B virus (HBV) characteristically induces a vigorous lymphomononuclear inflammatory response in the liver during acute and chronic hepatitis, it is possible that hepatocellular HBV gene expression may also be modulated by one or more of the cytokines produced by these cells. Using bacterial lipopolysaccharide (LPS) as a surrogate inducer of inflammatory cytokines in vivo, we have tested this hypothesis in a transgenic mouse model system. In experiments with two independent transgenic mouse lineages that express the HBV envelope region under the control of either HBV or cellular promoters, we observed a 50 to 80% reduction in the hepatic steady-state content of a 2.1-kb HBV mRNA following administration of a single intraperitoneal dose of LPS. The regulatory influence of several inflammatory cytokines known to be induced by LPS was also examined in this system. The negative regulatory effect of LPS was consistently reproduced by the administration of a single nontoxic dose of tumor necrosis factor alpha, and it was occasionally observed following the administration of high doses of alpha interferon and interleukin-6, while no effect was detectable in response to high-dose interleukin-1 alpha or to gamma interferon. These observations suggest that tumor necrosis factor alpha and perhaps other cytokines may activate a heretofore unsuspected intracellular pathway that negatively regulates HBV gene expression. The intracellular mechanism(s) responsible for this effect and its pathophysiologic relevance remain to be elucidated.
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PMID:Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice. 158 37

Several studies have shown that the cytokine interleukin-6 (IL-6) is produced in response to tumour necrosis factor (TNF) in vitro. This study examines the in vivo relation between these two cytokines with assays of plasma IL-6 and TNF levels in subjects with chronic hepatitis B undergoing immunomodulatory therapy with recombinant TNF (rTNF). Plasma IL-6 was detected from 20 min after rTNF infusion with levels peaking after 2-3 h and levels correlated with the dose of rTNF administered (r = 0.67, P = 0.004). Peak levels of IL-6 (mean 295, range 266-297 ng/l) were lower than those seen in certain disease states despite the very high peak levels of rTNF (mean 11,750, range 5623-18,620 ng/l). These findings suggest that the very high levels of IL-6 found in certain disease states are not purely the result of circulating TNF. Other factors such as endotoxin or other cytokines may also play a role in determining levels of plasma IL-6.
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PMID:Dose-dependent increase in plasma interleukin-6 after recombinant tumour necrosis factor infusion in humans. 226 82

Using our scoring system, we studied the production of monokines (interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6) by lipopolysaccharide-stimulated peripheral whole blood in 34 patients with chronic hepatitis C during the interferon-alpha/beta therapy. It decreased in 25.7% (9/35 group A), fluctuated in 60.0% (21/35, group B), and increased in 14.3% (5/35, group C). The patients in group A were younger than those in group B (P < 0.05). The histological grade of injury was milder in group A than in group B or C. The rate of sustained response was 66.7% (6/9) in group A, 19.0% (4/21) in group B, and 40.0% (2/5) in group C(P = 0.0184, group A versus group B). In summary, monokine production by peripheral whole blood varied during interferon therapy for chronic hepatitis C patients. No significant change was noted in 60% of the patients. However, patients with decreased monokine production were younger, with a mild histological grade, and likely to respond to the interferon therapy.
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PMID:Monokine production by peripheral whole blood in chronic hepatitis C patients treated with interferon. 758 25

Epidemiologic data indicate the crucial role of chronic hepatitis B virus (HBV) infection in hepatocellular carcinoma (HCC) development. On the molecular level, HBV sequences are frequently integrated in hepatocellular DNA. However, in contrast to the woodchuck model, in which specific HBV-DNA integration is detectable in most cases, insertional (in-) activation of cellular genes seems to be a rare event in man. The recent discovery of transactivating functions exerted by HBx and truncated HBs(urface) proteins supports the notion that transactivation of cellular gene expression could be relevant to hepatocarcinogenesis. HBV transactivator sequences are present in 81% (21/26) of HCC tissues or hepatoma-derived cell lines. At least one transactivator protein was functional in all cases investigated so far. The 16.5-kDa HBx transactivator has been shown to stimulate gene expression from various cellular target sequences. In vitro, HBx displays oncogenic potential. A second type of transactivator is encoded in the preS/S region of HBV. In contrast to HBx, HBs transactivators require carboxyterminal truncation to gain their transactivating function. Unlike full-length M(iddle)HBs, the truncated MHBst is retained in the endoplasmic reticulum and not secreted into the surrounding medium. Cellular gene expression is stimulated by regulatory elements of the human proto-oncogenes c-fos and c-myc, as well as by the hepatic acute-phase interleukin-6 gene. Synthetic binding sites for the transcription factors NF-kappa B, AP-1, AP-2, SRE, and Sp1 render minimal promoters activatable. NF-kappa B-mediated transactivation by MHBst can be suppressed by radical scavenging antioxidants, indirectly suggesting that reactive oxygen intermediates are involved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transactivation of cellular gene expression by hepatitis B viral proteins: a possible molecular mechanism of hepatocarcinogenesis. 760 73

This study was carried out to test the hypothesis that, in chronic hepatitis (CH), inflammatory processes, including viral replication, host immune response, and hepatocyte destruction, are regulated by a cytokine network in the liver. Expression of the mRNA of the cytokines IL1-beta, IL2, IL4, IL5, IL6, TNF-alpha, and IFN-gamma, the lymphocyte markers CD4 and CD8, and the HLA class I molecule, beta 2-microglobulin (B2MG) in the liver tissue of 20 CH(C) cases and 9 CH(B) patients was investigated by the reverse transcription polymerase chain reaction (RT-PCR) method. TNF-alpha, CD4, and B2MG mRNA were detected in 100% of cases of in both CH(B) and CH(C). The expression rates of IL1-beta, IL2, IL4, IFN-gamma, and CD8 mRNA were 80%, 40%, 25%, 40%, and 80% in CH(C) and 88.9%, 44.5%, 30%, 55.6%, and 100% in CH(B). IL6 mRNA was detected only in CH(B), in 22.2% of cases, IL5 mRNA was not detected in either CH(B) or CH(C). IL2, IL4, and IFN-gamma mRNA were expressed significantly more frequently in patients who had high serum ALT and a high histological activity index (HAI) score. There was no difference in cytokine expression between CH(B) and CH(C), except in IL6, suggesting the existence of a common immunopathogenesis for CH(B) and CH(C). In chronic viral hepatitis, IL1-beta and TNF-alpha appear to play a major role in immune responses and IL2, IL4, and IFN-gamma seem to be associated with increased cytotoxic T cell response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression rate of cytokine mRNA in the liver of chronic hepatitis C: comparison with chronic hepatitis B. 771 13

Recombinant human granulocyte-macrophage colony-stimulating factor therapy significantly reduces serum hepatitis B virus DNA levels, associated with increased 2',5'-oligoadenylate synthetase activity in cultured mononuclear cells of patients with chronic hepatitis B. To assess changes in immune function during therapy of chronic hepatitis B patients, spontaneous and mitogen-induced production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interferon-alpha and interferon-gamma were measured-along with serum levels of soluble CD4, soluble CD8, soluble interleukin-2 receptor and beta 2-microglobulin-before, during and after a 6-wk course of granulocyte-macrophage colony-stimulating factor in nine patients with chronic hepatitis B. Treatment statistically enhanced spontaneous production of tumor necrosis factor-alpha (p < 0.05) and interleukin-1 beta (p < 0.02). Furthermore, spontaneous interleukin-6 production correlated negatively with hepatitis B virus DNA levels (p < 0.03), and spontaneous interleukin-1 beta production correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.0005). In addition, statistically significant increases were found during therapy in serum levels of soluble interleukin-2 receptor (p < 0.01), soluble CD4 (p < 0.01) and beta 2-microglobulin (p < 0.05). Levels of soluble interleukin-2 receptor and soluble CD4 correlated negatively with levels of hepatitis B virus DNA (p < 0.05), and levels of soluble interleukin-2 receptor and beta 2-microglobulin correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.003 and p < 0.02, respectively). Thus recombinant human granulocyte-macrophage colony-stimulating factor administration may induce reductions in hepatitis B virus DNA levels, perhaps by altering the immune status and increasing cytokine production.
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PMID:Changes in cytokine production during therapy with granulocyte-macrophage colony-stimulating factor in patients with chronic hepatitis B. 792 47

To test the role of immune reactivity in the pathogenesis of hepatitis C, serum soluble immune factors were measured in a cohort of 57 patients with chronic hepatitis C, and in 20 healthy subjects. Levels of interleukin-1 beta, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-6 were detected in some, but not all, HCV patients and were in general undetectable in healthy subjects. Patients had significantly higher concentrations of neopterin (P = 0.0026), beta 2-microglobulin (P = 0.046), soluble interleukin-2 receptor (P = 0.021), and soluble CD8 (P < 0.039), than healthy controls; conversely, interferon-gamma levels were significantly lower (P = 0.023). Significant correlations were observed between beta 2-microglobulin concentration and Knodell's index (r = 0.638, P = 0.00045), the score of piecemeal necrosis (r = 0.572, P = 0.0023), and the degree of fibrosis (r = 0.527, P = 0.0056). Interleukin-2 levels correlated significantly with Knodell's index (r = 0.412, P = 0.037), and the degree of lobular cytolysis (r = 0.389, P = 0.048). According to therapeutic outcome, pretreatment levels of soluble CD8 were only significantly elevated (P = 0.042) in patients with a sustained biochemical response. On interferon-alpha treatment, the levels of beta 2-microglobulin, neopterin, and soluble interleukin-2 receptor increased significantly (P < 0.05), irrespective of therapy outcome. In summary, HCV patients have an altered immune reactivity that might play a role in the pathogenesis of chronic hepatitis C, and might influence the therapeutic outcome to interferon-gamma.
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PMID:Serum levels of soluble immune factors and pathogenesis of chronic hepatitis C, and their relation to therapeutic response to interferon-alpha. 795 20


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