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)

The host immune responses have been suggested to play a role in liver injury occurring in patients with chronic hepatitis C. In order to explore the relationship between the relative proportions of intrahepatic and peripheral blood lymphocytes (IHL, PBL), the levels of viremia, and the histological hepatitis activity score, three-color fluorescence-activated cytometric analysis was performed for 36 patients with chronic hepatitis C and six control subjects without chronic hepatitis. The liver biopsy was performed before any antiviral therapy. Each liver specimen was divided into two parts: one for histological examination and one for immunological analysis. Tricolor CD45 was used to improve "lymphogating." Fluorescein isothiocyanate- or phycoerythrin-conjugated monoclonal antibodies with specificity for CD3, CD4, CD8, and CD20 (lymphocyte subpopulations), for CD69 (activated lymphocytes), and for CD16/56 (natural killer cells) were used. The livers of patients with chronic hepatitis C contained a greater proportion of CD4+ lymphocytes that exhibited marked expression of CD69 than in control subjects (20.7 +/- 7.3% vs 10.2 +/- 4.6%, P = 0.027). Moreover, in patients with chronic hepatitis C, the proportion of CD4+ IHL correlated with the histological hepatitis activity evaluated by the Knodell score (r = 0.48, P = 0.004). No correlation was found between the percentage of CD4+ IHL and the level of viremia or transaminase activities. Our findings clearly indicate that a cellular immune response does take place in HCV-infected livers and could thus contribute to the outcome of hepatitis C virus infection.
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PMID:Phenotyping of intrahepatic and peripheral blood lymphocytes in patients with chronic hepatitis C. 944 Jun 26

We characterized liver-infiltrating leucocytes (LIL) from BALB/c and C57BL/6 mice 0-56 days after murine cytomegalovirus (MCMV) infection. Inflammation clears from C57BL/6 mice 4-5 weeks post infection (pi), but persists for several months in BALB/c mice. The LIL obtained were 60-80% Thy 1.2+ by flow cytometry. The percentage of CD8+ cells rose sharply in all mice 7 days pi, with little decrease in BALB/c mice by day 56. CD4-CD8-Thy 1.2+/TCR alpha beta + cells were more prevalent in LIL than lymph node cells (LNC) irrespective of MCMV infection, whilst infection increased the proportion of CD8+ L-selectin- LIL (but not LNC). LIL from both mouse strains demonstrated cytotoxic activity against YAC-1 cells, but only LIL from BALB/c mice proliferated spontaneously ex vivo 21 days pi, as measured by tritiated thymidine incorporation. BALB/c LIL produced IFN gamma and IgG2a 7-21 days pi, whilst IL-10 secretion was similar in both strains. Thus, persistent hepatitis in BALB/c mice is associated with activation and proliferation of intrahepatic leucocytes with some bias towards a Th1 response.
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PMID:Contrasting phenotypes of liver-infiltrating leucocytes isolated from MCMV-infected BALB/c and C57BL/6 mice. 961 48

C57BL/6 mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis several weeks after inoculation. Previously, we showed that mutations in the immunodominant CD8 T-cell epitope (S-510-518) could be detected in nearly all samples of RNA and virus isolated from these mice. These mutations abrogated recognition by T cells harvested from the central nervous systems of infected mice in direct ex vivo cytotoxicity assays. These results suggested that cytotoxic T-lymphocyte (CTL) escape mutants contributed to virus amplification and the development of clinical disease in mice infected with wild-type virus. In the present study, the importance of these mutations was further evaluated by infecting naive mice with MHV-JHM variants isolated from infected mice and in which epitope S-510-518 was mutated. Compared to mice infected with wild-type virus, variant virus-infected animals showed higher mortality and morbidity manifested by decreased weight gain and neurological signs. Although a delay in the kinetics of virus clearance has been demonstrated in previous studies of CTL escape mutants, this is the first illustration of significant changes in clinical disease resulting from infection with viruses able to evade the CD8 T-cell immune response.
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PMID:Infection with cytotoxic T-lymphocyte escape mutants results in increased mortality and growth retardation in mice infected with a neurotropic coronavirus. 962 Oct 53

Propagermanium is an organic germanium compound with immunopotentiating activity. We examined the hepatoprotective effect of propagermanium and its mechanism in an experimental animal model of acute liver injury induced with Corynebacterium parvum (C. parvum) and lipopolysaccharide (LPS) injection. Oral pretreatment with propagermanium decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in a dose-dependent manner. Significant attenuation of ALT and AST activity was obtained at a dose of 3 mg/kg. Administration of propagermanium also inhibited the infiltration of mononuclear cells into the liver of mice induced by C. parvum/LPS. Immunohistochemical examination revealed infiltration of the liver by CD4-, CD8-, CD11b- and Gr-1-positive cells. Propagermanium prevented CD4- and CD11b-positive cells from infiltrating the liver. In this animal model, blood cytokine levels increased rapidly after LPS injection, causing severe hepatitis. Notably, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the progress of liver injury. We demonstrated that propagermanium reduced IFN-gamma production by 53% at a dose of 3 mg/kg and also significantly inhibited the production of interleukin-12 (IL-12). These results indicate that propagermanium inhibits cell infiltration in the liver and cytokine production, and improves massive liver injury in C. parvum/LPS mice.
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PMID:Hepatoprotective effect of propagermanium on Corynebacterium parvum and lipopolysaccharide-induced liver injury in mice. 971 10

The liver injury in the concanavalin A (Con A)-induced mouse hepatitis model has been well studied. However, there has been little study on the effects of Con A on extrahepatic organs. The aim of the present work was to determine the effects of Con A on the spleen, kidney and lung. A histopathological study showed that Con A (15 mg/kg, i.v.) administration affects not only the liver, but also all these extrahepatic organs. Messenger RNA expression was studied by the using polymerase chain reaction. Treatment with Con A induced interleukin-2 mRNA in the spleen, but only slightly induced it in the kidney. The mRNAs of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were induced in all these organs. At 24 hr after Con A treatment, the expression of IFN-gamma mRNA, but not that of TNF-alpha mRNA, was inhibited by cyclosporine A (50 mg/kg, i.p.), suggesting that Con A induced these cytokine mRNAs through different mechanisms. In the kidney and lung, CD4+ and CD8+ T-cell infiltration was suggested by the Con A-induced CD4 and CD8 mRNAs. The present study showed the histopathological effects of Con A and Con A-induced cytokine mRNA expression on the spleen, kidney and lung.
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PMID:Expression of cytokine mRNA in extrahepatic organs in a mouse concanavalin A-hepatitis model. 971 69

In the present study, intrahepatic CD8+ lymphocyte infiltrates as well as HLA class I and CD54 (ICAM-1) antigen expression at both tissue and serum levels were evaluated in 54 untreated patients with chronic hepatitis C stratified on the basis of histological diagnosis (Chronic Persistent Hepatitis/Chronic Lobular Hepatitis -CPH/CLH- and Chronic Active Hepatitis -CAH-: 22 and 32 subjects, respectively). The relationships between soluble HLA-I (sHLA-I) and ICAM-1 (sICAM-1) serum levels and their membrane-bound counterparts, CD8+ liver infiltration and serum alanine aminotransferase (ALT) were also studied. A strong HLA-I and CD54 tissue expression, associated to the presence of CD8+ cell infiltrates in necro-inflammatory areas, and elevated sHLA-I and sICAM-1 serum amounts were observed in all patients. At the same time, no difference was found at tissue level between the two groups of patients with respect to the mean scores of HLA-I and CD54 expression, while CAH subjects displayed a significantly higher CD8 periportal and lobular reactivity in comparison to the other subset. Serological assays outlined higher values of circulating HLA-I molecules in CPH/CLH patients and higher sICAM-1 levels in the CAH group. Finally, a negative correlation was found between sHLA-I and ALT in CAH subjects while, in all patients, sICAM-1 positively correlated with both CD8 tissue infiltration and ALT. Our findings confirm the occurrence of an immune activation status during chronic hepatitis C and suggest that sHLA-I molecules might play a down-modulating role on immunoresponsiveness of these patients.
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PMID:Immunoresponsiveness in chronic hepatitis C patients: correlation between tissue and serum findings. 973 40

Little is understood of the anatomical fate of activated T lymphocytes and the consequences they have on the tissues into which they migrate. Previous work has suggested that damaged lymphocytes migrate to the liver. This study compares class I versus class II major histocompatibility complex (MHC)-restricted ovalbumin-specific T cell antigen receptor (TCR) transgenic mice to demonstrate that after in vivo activation with antigen the emergence of CD4(-)CD8(-)B220(+) T cells occurs more frequently from a CD8(+) precursor than from CD4(+) T cells. Furthermore, this change in phenotype is conferred only by the high affinity native peptide antigen and not by lower affinity peptide variants. After activation of CD8(+) cells with only the high affinity peptide, there is also a dramatically increased number of liver lymphocytes with accompanying extensive hepatocyte damage and elevation of serum aspartate transaminase. This was not observed in mice bearing a class II MHC-restricted TCR. The findings show that CD4(-)CD8(-)B220(+) T cells preferentially derive from a CD8(+) precursor after a high intensity TCR signal. After activation, T cells can migrate to the liver and induce hepatocyte damage, and thereby serve as a model of autoimmune hepatitis.
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PMID:Liver damage preferentially results from CD8(+) T cells triggered by high affinity peptide antigens. 974 33

Increased susceptibility to tuberculosis occurs in the alcoholic. One explanation for the altered susceptibility is a change in T-lymphocyte modulation. To evaluate this, 24 male and 24 female Sprague-Dawley rats were treated with either a Lieber-type liquid ethanol diet (LED) or an isocaloric control (LCD). After 2 weeks, half the subjects were infected with BCG (10(8) colony-forming units) and sacrificed after 42 days. Splenic helper (CD4) and suppressor/cytoxic (CD8) cells were quantitated by flow cytometry. By three-way analysis of variance, splenic cellularity was significantly increased by infection (p < 0.0001) but suppressed by LED (p = 0.0002). There was a marginal sexual difference (p = 0.065) with females exhibiting a 35% lower response while on alcohol. Examining lymphocyte subsets, the most significant changes were observed after infection (BCG) and alcohol treatment (LED). CD4 levels were diminished by LED (p = 0.0002) but markedly increased by infection (p < 0.0001), producing a highly significant interaction that affected both absolute number (p < 0.0001) and relative percent present (p = 0.0078). CD8 was influenced only by infection (p < 0.0001). This resulted in a infection-related increase in the CD4/CD8 ratio which was lower with LED (p = 0.0032). Splenic T-lymphocytes, predominately CD4, are involved in the host response to BCG hepatitis and are adversely influenced by LED, which may contribute to increased susceptibility.
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PMID:Host response to mycobacterial infection in the alcoholic rat: male and female dimorphism. 974 51

The administration of concanavalin A (Con A) (0.2 mg/mouse) into mice induced significant elevation of plasma alanine aminotransferase (ALT) at 8.5 hr after Con A treatment. CD8 mRNA, which is a marker of cytotoxic T-cell, was strongly induced at 16 and 24 hr after Con A treatment. Although pretreatment with cyclosporine A (CsA) (50 and 100 mg/kg, i.p.) inhibited Con A-induced elevation of plasma ALT, it did not inhibit Con A-induced CD8 mRNA expression. Morphological study revealed lymphoid cell infiltration in the liver, but the lymphoid cells were not present at the site of hepatocyte necrosis. These results suggest that Con A-induced CD8+ T-cell infiltration has a minimal effect in the development of hepatitis.
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PMID:Effects of concanavalin A treatment on CD8 mRNA expression in mouse liver. 980 70

Cell-mediated immune responses to hepatitis B (HBV) and hepatitis C virus (HCV) antigens are vigorous and multispecific in acute, self-limited infections. Moreover, the prevalent cytokine pattern of circulating virus-specific T cells from patients who recover spontaneously from acute hepatitis is Th1-like. Longitudinal analysis of the T cell response to HCV antigens from the early stages of HCV infection in patients who recover from hepatitis and those who do not indicates that weaker responses and a prevalent Th2 pattern of cytokine production is associated with viral persistence and chronic evolution of disease. Although similar sequential studies are missing in hepatitis B, the observation that HBV-specific T cell responses are very weak or totally undetectable in the peripheral blood of patients with long-lasting chronic hepatitis B suggests that strength and quality of virus-specific T cell responses at the early stages of infection may influence the final outcome of both hepatitis B and C. While T cell hyporesponsiveness seems to be an important determinant for HBV persistence once chronic hepatitis has developed, this mechanism appears to be less critical in chronic HCV infection, because the vigor and quality of HCV-specific T cell responses seem to improve as a function of the duration of infection. This is shown by the finding that HCV-specific CD4- and CD8-mediated responses are easily detectable in the peripheral blood of patients with long-lasting chronic hepatitis C and that production of Th1 cytokines predominates within their livers. HCV therefore seems to be able to persist even in the face of an active T cell response and to acquire the capacity to survive within a host environment apparently unfavorable to its persistence. The high variability of HCV may explain its efficiency in escaping immune surveillance.
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PMID:Antiviral cell-mediated immune responses during hepatitis B and hepatitis C virus infections. 1002 13


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