Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-gamma (IFN-gamma) appears to be important for the activation of T cells, and its binding to IFN-gamma receptors on T cells is an essential step for its actions. We investigated the expression of IFN-gamma receptors on T cells in chronic liver disease using radioiodinated recombinant interferon-gamma binding assay, and by Scatchard analysis. The mean numbers of IFN-gamma receptors on T cells from controls, asymptomatic hepatitis B virus carriers (ASC), patients with chronic active hepatitis (CAH), and patients with liver cirrhosis (LC) were 2,205 +/- 497, 2,494 +/- 1,074, 1,925 +/- 735, and 1,666 +/- 653, respectively. The numbers of IFN-gamma receptors on T cells from the patients with LC were significantly smaller than those of controls (P less than 0.05). Kids of IFN-gamma receptor on T cells from control and patient groups were 2.3 4.8 x 10(-9) M, and there was no significant difference among the groups. The percentage of T cells reactive with OKT3, OKT4, or OKT8 was similar in control and patient groups. These findings suggest that the decrease in IFN-gamma receptors in LC is not related to the activity of the liver damage, but is associated with the severity of the underlying disease. The normal expression of IFN-gamma receptors on T cells from CAH may provide a reasonable basis for IFN-gamma therapy to type B CAH.
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PMID:Interferon-gamma receptors on T cells in patients with chronic liver disease. 297 98

We investigated the role of the interferon system in the pathogenesis of chronic liver disease. Interferon-gamma production by peripheral blood mononuclear cells was measured with an ELISA. While concanavalin A-stimulated and recombinant interleukin 2-stimulated production of interferon-gamma in patients with chronic active hepatitis and liver cirrhosis was significantly decreased when compared with that of controls (518 +/- 189 and 729 +/- 195 units per ml, mean +/- S.D.), there was also a lot of overlap. Addition of indomethacin to the cultures partially restored interferon-gamma production in patients with chronic active hepatitis and liver cirrhosis, indicating that suppressor function of monocytes was, in part, responsible for the diminished interferon-gamma production. Serial studies showed that interferon-gamma production rose during acute deterioration of illness, during treatment with interleukin 2 and with the improvement of clinical course. Interferon-gamma production was not different among hepatitis B e antigen or antibody positive, and non-A, non-B patients with chronic active hepatitis and liver cirrhosis. Our findings suggest that diminished interferon-gamma production is associated with disease severity in chronic liver disease, irrespective of the hepatitis B virus carrier state. It would be interesting to compare the efficacy of treatment with interferon-gamma or interferon-gamma inducers such as interleukin 2 in chronic hepatitis B patients with and without decreased in vitro interferon-gamma production.
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PMID:Interferon-gamma production by peripheral blood mononuclear cells of patients with chronic liver disease. 310 84

Murine macrophages express high levels of nitric oxide synthase and produce large amounts of nitric oxide (NO) when stimulated with certain cytokines in the presence of a trace amount of lipopolysaccharide (LPS). The stimulatory cytokines include interleukin-1 (IL-1), interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and migration inhibitory factor. Activated macrophages are highly effective killers of intra- and extra-cellular pathogens. However, as excessive NO can lead to immunopathology (diabetes, graft-v.-host disease, EAE, liver cirrhosis, rheumatoid arthritis), NO production is necessarily under tight regulation. A number of cytokines, including IL-4, IL-10 and transforming growth factor-beta, can down regulate the induction of NO synthase in macrophages. In addition, macrophages exposed to LPS alone and then stimulated with a mix of IFN-gamma and LPS express significantly lower levels of NO synthase than cells stimulated without pre-exposure to LPS. Furthermore, NO can reduce the activity of NO synthase by feedback inhibition, and also inhibit the production of IFN-gamma by Th1 cells (thus turning off its own synthesis from upstream). The regulatory pathways involve tyrosine kinase and protein kinase C.
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PMID:The role of nitric oxide in parasitic diseases. 751 Jan

Cell growth appears to be controlled by positive and negative cell growth regulation. Little is known about the growth regulation of hepatocytes in the cirrhotic liver. Clarifying the responses of hepatocytes obtained from cirrhotic liver to various growth factors and growth inhibitory factors might aid understanding of alterations in growth regulation of the hepatocytes in the cirrhotic liver. We investigated the effects of hepatocyte growth factor, epidermal growth factor, heparin-binding epidermal growth factor-like growth factor, transforming growth factor-beta 1, interferon-alpha and interferon-gamma on the DNA synthesis of hepatocytes from cirrhotic and normal rats in primary culture. Cirrhosis was induced in male Sprague-Dawley rats by means of oral administration of 0.05% thioacetamide in drinking water for 4 mo. Hepatocytes were isolated by means of an in situ perfusion method, and DNA synthesis was assessed from the amount of DNA-incorporated [3H]thymidine. Stimulation of the DNA synthesis of hepatocytes by hepatocyte growth factor, epidermal growth factor and heparin-binding epidermal growth factor-like growth factor was not different between normal and cirrhotic rat liver. Transforming growth factor-beta 1 inhibited the DNA synthesis of hepatocytes in both. However, the concentration of transforming growth factor-beta 1 giving a 50% inhibition of DNA synthesis was about two times higher in cirrhotic hepatocytes (0.11 ng/ml) than in normal hepatocytes (0.06 ng/ml). In cirrhotic hepatocytes, the expression of transforming growth factor-beta type II receptor gene was about 50% of that in normal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alteration in growth regulation of hepatocytes in primary culture obtained from cirrhotic rat: poor response to transforming growth factor-beta 1 and interferons. 752 74

Chronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse chronic sequalae such as cirrhosis and hepatocellular carcinoma. Over the past 20 years, many antiviral or immunomodulatory agents, or both, have been used in patients with chronic HBV infection. Among immunomodulatory agents, levamisole, BCG, picibanil and interleukin-2 have been shown to be ineffective. Corticosteroid therapy is also ineffective and can cause deleterious effects in chronic HBV infection. Thymosin-alpha 1 therapy is currently in phase III clinical trial. Among antiviral agents, acyclovir, dideoxynucleosides, suramin, zidovudine and ganciclovir have been shown to be ineffective and have intolerable side effects. While adenine arabinoside (Ara-A) and its monophosphate derivative (Ara-AMP) are effective agents if the treatment course is long enough, they have been withdrawn from investigative use because of their substantial neuromuscular toxicity. Interferon-alpha may directly inhibit HBV replication and enhance hepatocyte HLA class I antigen expression with subsequent increase of T-cell mediated cytotoxicity. Randomized, controlled clinical trials have shown that 25% to 50% of adult patients with elevated alanine transaminase (ALT) levels lost HBeAg and HBV-DNA when treated with IFN-alpha at a dose of 5MU daily or 10 MU three times a week for 3 to 6 months. In view of the fact that the response rate is far from satisfactory, particularly in Asian patients, combination therapies including interferon alpha with Ara-AMP, acyclovir, didoxynucleoside or interferon-gamma have been studied. Most forms of combination therapy have been shown to be of limited effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Drug therapy in patients with chronic type B hepatitis]. 754 84

Hepatocellular carcinomas 1 cm in diameter with high or low echogenicity can be detected on ultrasonography and confirmed on fine-needle biopsy, but it is still very difficult to detect small hepatocellular carcinomas with isoechogenicity. In this study, we assessed lymphokine-activated killer cell activity and interferon-gamma production prospectively every 1 to 3 mo for 23 +/- 4 mo (mean +/- 1 S.D.) in 227 patients with cirrhosis. Transient depression of lymphokine-activated killer activity was detected in 43 patients (defective lymphokine-activated killer group), and hepatocellular carcinoma was detected in 24 cases before the end of the 18-mo follow-up. Twenty-one (87.5%) of the 24 hepatocellular carcinoma patients were included in the defective lymphokine-activated killer group. Defective lymphokine-activated killer activity was detected more than 6 mo before detection of a space occupying lesion in the liver or elevation of alpha-fetoprotein level above 400 ng/ml. Serum alpha-fetoprotein level was elevated above 400 ng/ml in only five cases in which hepatocellular carcinoma was detected as a space-occupying lesion. Our results indicate that sequential assessment of lymphokine-activated killer activity may be a predictor of hepatocellular carcinoma and that the depression of immune function in cirrhotic patients is a serious risk factor for hepatocellular carcinoma emergence.
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PMID:Depressed immune function in patients with cirrhosis before emergence of hepatocellular carcinoma. 768 81

Approximately 5% of the world population is infected by the hepatitis B virus (HBV) which causes a necroinflammatory liver disease of variable duration and severity. Chronically infected patients with active liver disease carry a high risk of developing cirrhosis and hepatocellular carcinoma. The immune response to HBV-encoded antigens is responsible both for viral clearance and for disease pathogenesis during this infection. While the humoral antibody response to viral envelope antigens contributes to the clearance of circulating virus particles, the cellular immune response to the envelope, nucleocapsid and polymerase antigens eliminates infected cells. The class I- and class II-restricted T cell responses to the virus are vigorous, polyclonal and multispecific in acutely infected patients who successfully clear the virus, and they are relatively weak and more narrowly focussed in chronically infected patients who do not. The pathogenetic and antiviral potential of the cytotoxic T lymphocyte (CTL) response to HBV have been demonstrated by the induction of a severe necroinflammatory liver disease following the adoptive transfer of HBV surface antigen-specific CTL into HBV transgenic mice, and by the noncytolytic suppression of viral gene expression and replication in the same animals by a post-transcriptional mechanism mediated by interferon-gamma, tumor necrosis factor-alpha and interleukin-2. The dominant cause of viral persistence during HBV infection is the development of a weak antiviral immune response to the viral antigens. While neonatal tolerance probably plays an important role in viral persistence in patients infected at birth, the basis for poor responsiveness in adult onset infection is not well understood and requires further analysis. Viral evasion by epitope inactivation and T cell receptor antagonism may contribute to the worsening of viral persistence in the setting of an ineffective immune response, as can the incomplete down-regulation of viral gene expression and the infection of immunologically privileged tissues. Chronic liver cell injury and the attendant inflammatory and regenerative responses create the mutagenic and mitogenic stimuli for the development of DNA damage that can cause hepatocellular carcinoma. Elucidation of the immunological and virological basis for HBV persistence may yield immunotherapeutic and antiviral strategies to terminate chronic HBV infection and reduce the risk of its life-threatening sequellae.
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PMID:Hepatitis B virus immunopathology. 857 Nov 72

We previously reported that interferon-gamma (IFN-gamma) production by PBMC in response to HCV core protein was increased in patients with type C chronic liver disease. To understand better the pathophysiology of this disease, we evaluated production of IL-10 and IL-12 by PBMC from 41 patients with chronic HCV infection, including asymptomatic HCV carriers with persistently normal serum ALT values. IL-10 is known to inhibit many effector functions of the immune system, suppressing Th1-type cell development, while IL-12 stimulates differentiation of Th1-type cells, facilitating cell-mediated immunity. IL-10 production was determined by culturing lymphocytes with concanavalin A (Con A), while IL-12 was produced by monocytes in the presence of Staphylococcus aureus Cowan 1 (SAC) with or without recombinant HCV core protein, respectively. The cytokine levels in culture supernatants were measured by ELISA. Spontaneous IL-10 production was greater in patients with chronic hepatitis (CH) (229 +/- 119 pg/ml, P < 0.01) and liver cirrhosis (LC) (185 +/- 88 pg/ml, P < 0.05) than in controls (119 +/- 27 pg/ml), while it was decreased during IFN treatment (70 +/- 25 pg/ml). Both HCV core protein and Con A enhanced IL-10 production by cells from HCV-infected patients. IL-12 was not detectable in medium alone cultures, and SAC-induced IL-12 production did not differ between various patient groups and controls. Simultaneous addition of HCV protein resulted in an increase of IL-12 production in chronic liver disease compared with SAC-alone cultures. Addition of IL-10 to the cultures equally suppressed IFN-gamma production for both controls and patient groups, but the enhancing effect of IL-12 on IFN-gamma production was significantly less in LC than in controls and other patient groups. The findings suggest that secretion of IL-10/IL-12 by cells from control individuals and various patient groups may be different, and that the cytokines might show different effects on IFN-gamma production by some cells.
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PMID:Production of interleukins 10 and 12 by peripheral blood mononuclear cells (PBMC) in chronic hepatitis C virus (HCV) infection. 909 22

The study was conceived to evaluate if S-adenosil-L-methionine, a substance commonly used in the treatment of cholestasis in patients with cirrhosis and chronic hepatitis, exerts any immunological effect and of it is able to counterbalance bile acid-mediated immunosuppression. Proliferation and interleukin 2 and interferon-gamma secretion of human lymphocytes, collected from healthy subjects and exposed to mitogenic stimuli (phytohemagglutinin, pokeweed and anti-CD3 monoclonal antibodies), were analysed in the basal condition or after exposure to S-adenosil-L-methionine and/or chenodeoxycholic acid. Chenodeoxycholic acid inhibited phytohemagglutinin-induced lymphocyte proliferation and interferon-gamma secretion, and phytohemagglutinin and pokeweed-mediated interleukin 2 secretion. S-adenosil-L-methionine did not affect lymphocyte proliferation while it reduced interleukin 2 secretion upon phytohemagglutinin and pokeweed stimulation and interferon-gamma secretion upon all stimuli tested. Moreover, S-adenosil-L-methionine counteracted chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2 secretion. The results of our study confirm the immunosuppressive role of chenodeoxycholic acid on both secretive and proliferative lymphocyte functions and provide evidence of immunomodulatory activities of S-adenosil-L-methionine and its capacity to antagonize chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2 secretion.
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PMID:S-adenosil-L-methionine is able to reverse the immunosuppressive effects of chenodeoxycholic acid in vitro. 930 55

We measured the activity of adenosine deaminase (ADA) and the concentration of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the pleural effusions from 28 patients with tuberculosis, 30 with neoplastic diseases, 25 with bacterial infections and 18 with congestive heart failure or liver cirrhosis. The levels of ADA (83.0 +/- 32.1 IU/L) and IFN-gamma (795.0 +/- 666.4 pg/ml) in tuberculous effusions were significantly higher than those in other groups (p < 0.0001). IL-1 beta level in the effusions of bacterial infections (265.2 +/- 379.2 pg/ml) was higher than that in other groups (p < 0.0001). TNF-alpha level in the effusions of tuberculosis (31.7 +/- 36.7 pg/ml) and bacterial infections (69.5 +/- 232.9 pg/ml) was higher than that in other groups. IL-8 level of exudative effusions was higher than that of transudates. IL-2 was only present in 4 effusions from tuberculosis and 1 effusion from bacterial infections. Diagnostic utilities of cytokines and ADA for tuberculous effusion were evaluated using receiver operating characteristics (ROC) curve analysis. The cut-off points of ADA, IL-1 beta, IL-8, TNF-alpha and IFN-gamma determined in this analysis were 54 IU/L, 5.5 pg/ml, 405 pg/ml, 4.5 pg/ml and 28 pg/ml, respectively and the sensitivity and the specificity of them were 88.0% and 95.9%, 19.1% and 74.1%, 57.1% and 63.2%, 81.0% and 77.2%, and 96.2% and 98.5%, respectively. In ADA, TNF-alpha and IFN-gamma, the areas under the curve (AUC) that represent the diagnostic accuracy were 0.968, 0.719 and 0.993, respectively. AUC of IFN-gamma was significantly higher than that of ADA or TNF-alpha. In tuberculous pleural effusion, IFN-gamma was significantly correlated with TNF-alpha, IL-1 beta and ADA. The correlation was also present between TNF-alpha and ADA.
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PMID:[Clinical significance of cytokine measurement in pleural effusion]. 938 55


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