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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines constitute a complex network of molecules involved in the regulation of the inflammatory response and the homeostasis of organ functions. Cytokines coordinate physiologic and pathologic processes going on in the liver, such as liver growth and regeneration, inflammatory processes including viral liver disease, liver fibrosis and cirrhosis. Liver growth and regeneration are regulated by several cytokines. The platelet-derived hepatocyte growth factor, in particular, delivers a strong mitogenic stimulus for hepatocyte regeneration. The cell-mediated immune response plays a central role in hepatocellular necrosis and in the immunopathogenetic mechanisms involved in viral clearance and persistence in liver disease of viral etiology. In this context, cytokines modulate the immune system and exert direct antiviral activity by cytopathic and non-cytopathic mechanisms, as demonstrated in a transgenic mouse model. IL-6, TNF-alpha, IL-1 and IL-2 increase in acute fulminant viral hepatitis; in fact, they have pro-inflammatory and cytotoxic effects. Reduced IL-2 and IFN-alpha synthesis and increased serum levels of IL-1 and IL-2 soluble receptor (IL-2R) have been observed in HBV chronic liver disease. In HCV chronic hepatitis, IL-2R increases as well, while IFN-gamma and IL-2 decrease. In personal experimental observations, intra-hepatic messenger RNA expression of several cytokines was measured in liver specimens of patients with chronic HBV and HCV infections: patients with HCV chronic liver disease had higher levels of IL-2, IL-6, IL-10, and IFN-gamma. These data are in accordance with immunological studies showing a vigorous cell-mediated immune response in HCV chronic liver disease and a deficient immune response in HBV chronic hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cytokine mediators in acute inflammation and chronic course of viral hepatitis]. 772 1

Anti-interleukin-4 (IL-4) treatment of Schistosoma japonicum-infected mice markedly inhibited in vitro secretion of the Th2 cytokines IL-4 and IL-5 from antigen-stimulated spleen cells, but enhanced the secretion of the Th1 cytokine IFN-gamma. IL-2 secretion was unaffected. Hepatic fibrosis was markedly diminished in anti-IL-4-treated-mice at ten weeks of infection while granulomas around S. japonicum eggs in the livers were slightly-to-moderately increased in size. The number of eggs per worm pair in the tissues and feces did not differ significantly in treated and untreated mice. These findings suggest that Th2 cytokine responses are important in the genesis of schistosomal hepatic fibrosis.
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PMID:Anti-interleukin-4 treatment diminishes secretion of Th2 cytokines and inhibits hepatic fibrosis in murine schistosomiasis japonica. 776 Nov 7

Inbred CBA/J mice with chronic (20-week) Schistosoma mansoni infections demonstrate two distinct syndromes. Hypersplenomegaly syndrome (HSS), characterized by a massive spleen, liver fibrosis, ascites, and anemia, resembles hepatosplenic human schistosomiasis, complete with portal hypertension and shunting. Moderate splenomegaly (MSS) syndrome, with less severe pathology, parallels most chronic human infections. Phenotypic analyses of spleen cells for CD44, CD62L, CD45RB, Ia, and CD25 indicate that HSS mice have more activated and memory CD4+ T cells than do MSS mice. HSS animals also have more B cells that highly express B7-2. Anti-CD3 stimulated spleen cells from 8-week or chronically infected mice produce IL-4 and IL-10 in a manner that appears not to involve the CD28/B7-2 costimulation pathway. By contrast IFN-gamma production is augmented in the presence of anti-CD28 and decreased in the presence of anti-B7-2. Infected mice make very little IL-2 to anti-CD3, even with added anti-CD28. As cytokines affect resultant B-cell responses and HSS and MSS mice display distinctive isotypes, differential regulatory or anergy hypotheses may best explain MSS/HSS differences.
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PMID:Immunopathogenesis and immunoregulation in schistosomiasis. Distinct chronic pathologic syndromes in CBA/J mice. 899 59

Colchicine in a dose of 200 micrograms kg body weight/day (5 days/week) was administered to groups of Schistosoma mansoni infected mice 12 weeks post infection, either alone or following previous praziquantel therapy at the 8th week of infection. Certain groups received colchicine for 6 weeks and others received it for 10 weeks. Colchicine alone did not significantly change the light microscopic appearance of schistosomal liver fibrosis, or hepatic collagen content estimated histomorphometrically, and did not reduce the elevated IL-2 serum level. Colchicine induced hepatic injury consisted of intense inflammatory reaction in granuloma and portal tracts, hepatocytic degeneration, and elevation of serum AST and ALT levels. Colchicine seemed to postpone granulomatous reaction healing and collagen deposition rather than inhibiting collagen formation or degrading it. Colchicine inhibited proliferation of hepatocytes of infected mice by expanding G2-M phases of cell cycle, thus reduced Ag NOR count and raised cell ploidy and cyclic AMP serum level. Subsidence of schistosomal infection by praziquantel prior to colchicine therapy greatly reduced inflammatory cellular reaction, significantly diminished hepatic collagen deposition and serum IL-2 level, minimized the elevated nuclear ploidy and cyclic AMP serum level that followed colchicine therapy when administered alone.
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PMID:Colchicine therapy for hepatic murine schistosomal fibrosis: image analysis and serological study. 1036 84

Hepatic fibrosis is a common outcome of chronic liver diseases. In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to fibrosis, which is immunologically characterized by the dominant Th2 response. Recently, it has been shown that gene therapy is an attractive approach for the treatment of hepatic fibrosis. To investigate the antifibrotic effects of IL-18 gene transfer, a normal murine liver cell line BNL.CL2 was transfected with recombinant adenovirus encoding mouse IL-18, and then intrasplenically transplanted into mice infected with Schistosoma japonicum (S. japonicum). Our data show that IL-18 gene-modified hepatocytes intrasplenically transplanted into mice can effectively express IL-18 in the liver and in peripheral blood. Intrasplenic transplantation of IL-18 gene-modified hepatocytes into S. japonicum-infected mice could result in a significantly increased IFN-gamma and IL-2 but decreased IL-4 and IL-10 concentration both in the liver and in the serum, suggesting that the dominant Th2 response in mice with schistosomiasis could be reversed by this intervention. Consistent with the changes in Th1 and Th2 cytokine production, mice intrasplenically transplanted with IL-18 gene-modified hepatocytes developed much less hepatic fibrosis at 20 weeks after infection, which was evaluated by liver content of hydroxyproline, collagens, and hepatic mRNA expression of procollagens. These data indicate that intrasplenic transplantation of IL-18 gene-modified hepatocytes can be a candidate for therapeutic intervention in hepatic fibrosis through induction of a dominant Th1 response.
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PMID:Intrasplenic transplantation of IL-18 gene-modified hepatocytes: an effective approach to reverse hepatic fibrosis in schistosomiasis through induction of dominant Th1 response. 1157 70

Although several mouse models of AIH have been described, no model is ideal. Indeed, the disease is self-limited in each model, and none is associated with significant liver fibrosis or progression to cirrhosis. Nevertheless, these models should be useful for testing different hypotheses regarding the initiation of AIH. Still, each model poses unique limitations. The EAIH model initiated by immunization with crude liver antigens in CFA has been plagued by a high prevalence of hepatitis lesions in CFA controls and inconsistencies in results. The TGF beta-1 and IL-2 deficient models lead to high in utero mortality and short median life spans in the surviving animals. Lastly, all models require more detailed characterization of the antigen specificity of infiltrating liver T cells and the pathogenesis of liver cell injury.
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PMID:Animal models of autoimmunity. 1236 80

Schistosoma mansoni is the most prevalent cause of liver fibrosis in Egypt. It is characterized by hepatocyte damage, inflammation and chronic parasite egg-induced granuloma formation leading to fibrosis. Its management, particularly fibrosis, has focused primarily on treating and preventing the complications of portal hypertension. Unfortunately, there is no therapy that has been proved to prevent progressive hepatic fibrosis which is associated with a significant morbidity and mortality due to granulomatous hypersensitivity to parasite eggs. However, recent developments in understanding hepatic fibrogenesis confirm that recovery from advanced fibrosis is possible. There is a considerable imperative to develop anti-fibrotic strategies that are applicable to liver fibrosis. It was noted that a marked increase in the amount of different interstitial collagens types are associated with the development of fibrotic liver diseases. Meanwhile, it has been suggested that as long as the relative portions of liver collagen are still within the normal limits, the fibrosis may still be reversible. If it exceeds the normal limits fibrogenesis will proceed to its end stage, even if the etiological agent is removed. Collagen type IV and procollagen type III are two of the most accurate fibrosis markers which allow reliable non-invasive diagnosis. The T lymphocytes and the immuno-regulatory cytokines may be important in the host response to S. mansoni granuloma formation and fibrosis. Chronic parasite egg-induced granuloma formation can lead to fibrosis, which is immunologically characterized by the dominant Th2 response. Corticosteroids and prostaglandins interfere with both efferent and afferent mechanisms of immune function. These data indicate that this adjuvant therapy can be a candidate for therapeutic intervention in hepatic fibrosis through induction of a balance between Th1 and Th2 cells response as will be documented by the fibrosis markers. One hundred S. mansoni infected hamsters (150-250 gm) were obtained from the BRPU-TBRI (5 groups, 20 hamsters each). Treatment was started 10 weeks post infection. First G (20 hamsters) was neither infected nor treated, second G. was infected but untreated, third group infected and PZQ treated, forth G. infected and PZQ and MP treated and fifth group infected and PZQ and PgE1 treated. Samples (liver and blood) were obtained 20 weeks post infection. The serum level of: liver functions, procollagen type III, collagen type IV & Th1 cytokine (IL-2) and Th2 cytokine (IL-10) were performed. Histopathology was performed to study liver fibrosis, measuring the proliferate activity of the hepatocytes using cell image analyzer system and granuloma cells using the indirect immuno-histochemistry by monoclonal antibody proliferating cell nuclear antigen (PCNA). In this study, G.V showed high significant reduction in granuloma size, type and percentage of fibrosis and significant elevation in percentage of degenerated ova compared to Gs.III & IV. The proliferation index measured using PCNA showed high proliferative activity of hepatocytes in non treated group which declined in the treated Gs.III, IV & V. The proliferation activity of hepatocytes and granuloma forming cells decreased significantly in G.V compared to G.IV. There was a significant reduction in liver function tests even tendency for normalization in G.V compared to group III and IV. Procollagen type III and collagen type IV were significantly low in the serum in G.V compared to Gs.III & IV. Th1 (IL-2) level was significantly high in G.V compared to Gs.III, IV and Th2 (IL-10) was significantly low in G.V compared to Gs III & IV indicating the low amount of fibrosis was in the group treated with PZQ PgE1.PgE1 with PZQ to treat S. mansoni infected hamsters can modulate liver fibrosis and improves the liver function tests up to normalization. The balance between Th1 and Th2 cytokines level could be modulated to help reverse or decrease fibrosis in S. mansoni infected hamsters. This may pave the way for clinical application as combined therapy PZQ and PgE1 may by an effective approach to reverse hepatic fibrosis in schistosomiasis by the induction of dominant Th1 response.
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PMID:The pharmacological approach to reverse portal hypertention and hepatic schistosomal fibrosis in Egypt, control experimental study. 1633 84

HCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients. IFN-gamma and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCV-derived peptides. We observed that HCV-specific T-cell responses were polyfunctional in HCV mono-infected patients, with presence of proliferating single IL-2-, dual IL-2/IFN-gamma and single IFN-gamma-producing CD4+ and dual IL-2/IFN-gamma and single IFN-gamma-producing CD8+ cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV co-infected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4+ and dual IL-2/IFN-gamma-producing CD8+ T cells. In addition, HCV-specific proliferation of CD4+ and CD8+ T cells was severely impaired in HIV/HCV co-infected patients and liver transplant recipients. Importantly, "only effector" T-cell responses were associated with significantly higher HCV viral load and more severe liver fibrosis scores. Therefore, the present results suggest that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 co-infection and liver transplantation.
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PMID:Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication. 1895 74

Hepatitis, a common human disease, may be followed by severe liver injury, eventually leading to fatty liver, liver fibrosis and hepatocellular carcinoma. CD8 T cells are a double-edged sword in the response to infection with the hepatitis virus. On one hand, rapid activation of CD8 T cells is critically important for the elimination of the virus. On the other hand, in persistent viral infection, the activation of CD8 T cells substantially contributes to liver injury. The clinical course of hepatitis, thus, critically depends on mechanisms regulating the activity of CD8 T cells. In observations in human hepatitis and in mice infected with the lymphocytic choriomeningitis virus, the clinical course of hepatitis is modified by several immunological factors including neutralizing antibodies: RIG-I, TLRs, MyD88, interferon type I, TNF-alpha, MHC I, Tap, TCR, CD8, IL-2, IL-7, PD-1, IFN-I, IL-10, IFN-gamma, perforins, serotonin and iNOS (table 1) . Additional experimental effort is needed to understand the concerted interplay of those molecules in viral hepatitis of man and mice.
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PMID:Host mechanisms in viral hepatitis. 2046 Aug 87

The liver fluke Clonorchis sinensis (Digenea) is a high-risk parasite that causes serious diseases such as cirrhosis, carcinogenic liver damage and clonorchiasis in East Asia. This study was conducted to evaluate the relationship between stress/endocrine hormones and inflammation induced by infection as well as the expression of heat shock proteins (hsp-27, hsp-90), cox-2 and cytokines in the livers of hamsters infected with C. sinensis. The average body weight of infected hamsters decreased up to 25% compared with that of the control group, and bile duct hyperplasia with inflammation, liver fibrosis and hepatic necrosis were observed in C. sinensis-infected livers. The expression of hsp-27, hsp-90, and cox-2 was significantly increased in the livers of C. sinensis-infected hamsters compared with the control group. Moreover, the expression levels of inflammatory cytokines (IL-1beta, IL-2, TGF-beta2 and IFN-alpha1) were markedly increased in the livers of the infected group compared with those of the control group. Consistently, plasma IL-3 and IL-6 levels gradually increased during the infection period, and the concentration levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), corticosterone, and adrenocorticotropic hormone (ACTH) in C. sinensis-infected hamsters increased over 25%, compared with those of the uninfected normal group. These results demonstrate that C. sinensis infection may increase the expression of hsp27, hsp90 and cox-2 as well as it may cause periductal fibrosis, chronic inflammation and hepatic necrosis in the liver. Furthermore, the results indicate that C. sinensis infection induces not only stress-induced hormone imbalance but also the sustained secretion of inflammatory cytokines through chronic stress/stimuli.
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PMID:The characteristics of the expression of heat shock proteins and COX-2 in the liver of hamsters infected with Clonorchis sinensis, and the change of endocrine hormones and cytokines. 2332 6


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