Lack of evidence for the Th2 predominance in patients with chronic hepatitis C

Bergamini, Alberto; Bolacchi, Francesca; Cerasari, G.; Carvelli, C; Faggioli, Emanuela; Cepparulo, Mario; Demin, F.; Uccella, Ilaria; Bongiovanni, Barbara; Niutta, P.; Capozzi, M.; Lupi, M.; Piscitelli, Elisabetta; Rocchi, G; Angélico, M.

doi:10.1046/j.1365-2249.2001.01467.x

Cited by 14 publications

(13 citation statements)

References 48 publications

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“…Regarding cytokine responses to persistent HCV infection, past reports in diversified patient groups were rather inconsistent: enhanced T H 1 responses [26 -29], T H 2 responses [30 -32], or both types [33,34]. Although differing degrees of pathogenesis and/or inflammation among study patient groups may be in part responsible for this discrepancy [34,35], some potential methodological drawbacks in studies demonstrating T H 2 cytokine predominance were indicated [27]. The present study on lymphocyte subsets suggested enhanced T H 1 immunity in persistent HCV infection, supporting a view that enhanced T H 1 immunity alone is not sufficient to regulate the virus in many cases of HCV infection.…”

Section: Discussionmentioning

confidence: 93%

Lymphocyte subset characterization associated with persistent hepatitis C virus infection and subsequent progression of liver fibrosis

et al. 2011

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This study aims to deepen the understanding of lymphocyte phenotypes related to the course of hepatitis C virus (HCV) infection and progression of liver fibrosis in a cohort of atomic bomb survivors. The study subjects comprise 3 groups: 162 HCV persistently infected, 145 spontaneously cleared, and 3,511 uninfected individuals. We observed increased percentages of peripheral blood T(H)1 and total CD8 T cells and decreased percentages of natural killer (NK) cells in the HCV persistence group compared with the other 2 groups after adjustment for age, gender, and radiation exposure dose. Subsequently, we determined that increased T(H)1 cell percentages in the HCV persistence group were significantly associated with an accelerated time-course reduction in platelet counts-accelerated progression of liver fibrosis-whereas T(C)1 and NK cell percentages were inversely associated with progression. This study suggests that T(H)1 immunity is enhanced by persistent HCV infection and that percentages of peripheral T(H)1, T(C)1, and NK cells may help predict progression of liver fibrosis.

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Section: Discussionmentioning

confidence: 93%

Lymphocyte subset characterization associated with persistent hepatitis C virus infection and subsequent progression of liver fibrosis

et al. 2011

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“…Although the dominance of Th2 cytokines in HCV patients is not sufficient for the establishment of chronic infection, 78,79 the development of chronic HCV infection has been linked to a weak or absent Th1 response and the presence of Th2 cytokines. 31,32,34,35,80,81 In addition, clearance of chronic HCV infection upon IFN-␣ treatment is associated with a shift from a Th2-dominant to a Th1-dominant phenotype.…”

Section: Therapeutically Relevant Concentrations Of Ifns Differentialmentioning

confidence: 99%

Immunomodulatory Activities of IFN-γ1b in Combination with Type I IFN: Implications for the Use of IFN-γ1b in the Treatment of Chronic HCV Infections

Wang¹,

Blatt²,

Seiwert³

2006

Journal of Interferon & Cytokine Research

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The standard of care for chronic hepatitis C, pegylated interferon-alpha (IFN-alpha) and ribavirin (RBV), causes a sustained virologic response (SVR) in approximately 50% of patients. SVR is correlated with innate and adaptive immune system responses, such as natural killer (NK) cell activation, production of IFN-alpha from immature plasmocytoid dendritic cells (pDC), and polarization of CD4(+) cells to a T helper 1 (Th1) cell phenotype. To examine how these immunologic responses vary with currently available regimens for chronic hepatitis C, cell populations purified from human peripheral blood mononuclear cells (PBMC) were treated with the clinically available combinations of pegylated IFN-alpha2b (PEG-IFN-alpha2b) + RBV, IFN-alphacon1 + RBV, or IFN- alphacon1 + IFN-gamma1b, and activation of cellular immune system components was monitored. The magnitude of NK cell activation depended on regimen, with IFN-alphacon1 + IFN-gamma1b > IFN-alphacon1 + RBV > PEG-IFN- alphaa2b + RBV. The maximum human serum concentrations of IFN-alphacon1 + IFN-gamma1b saturated NK cell activation, whereas the maximum human serum concentrations of IFN-alphacon1 + RBV or PEG-IFN-alpha2b + RBV did not. IFN-gamma1b also enhanced the production of IFN-alpha from immature pDCs, which are the dominant source of IFN-alpha upon viral infection. The rank order for induction of Th1 cell phenotype and repression of Th2 cell phenotype by the cocktails described was identical to that observed for NK cell activation. Additionally, IFN- gamma1b suppressed the ability of the hepatitis C virus (HCV) NS4 protein to enhance monocyte secretion of interleukin- 10 (IL-10), a cytokine whose expression level is correlated with viral persistence. These results suggest that addition of IFN-gamma1b to HCV treatment regimens may provide unique benefits.

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“…Thus in addition, data suggest that a dysregulation exists in the peripheral CD4 + T‐cell population such that inappropriate cytokines are made in response to viral antigens accounting for viral persistence and evolution of chronic disease. However, the results of the different studies are conflicting in respect to the predominating TH1 or TH2 cytokine response resulting in the inability of the host to terminate HCV infection [12–23].…”

Section: Introductionmentioning

confidence: 99%

Cytokine mRNA expression in hepatitis C virus infection: TH1 predominance in patients with chronic hepatitis C and TH1–TH2 cytokine profile in subjects with self‐limited disease

Gigi

Raptopoulou‐Gigi

Kalogeridis

et al. 2007

Journal of Viral Hepatitis

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Many determinants of the immune response have been implied in the pathogenesis of chronic hepatitis C. TH1 and TH2 cytokines play a prominent role in viral infections and a dysregulation of these cytokines could account for viral persistence and evolution of chronic disease. To explore a possible TH1 and TH2 cytokine dysregulation resulting in the inability to terminate hepatitis C virus (HCV) infection, we studied TH1 [interferon (IFN)-gamma, interleukin (IL)-2] and TH2 (IL-4, IL-10) mRNA expression of peripheral blood mononuclear cells (PBMC) in response to NS3 HCV antigen stimulation, in 31 untreated patients with chronic hepatitis C and 29 subjects with self-limited disease. After a 48 h culture of PBMC, total RNA isolation was performed and complementary DNA was prepared by reverse transcription. mRNA levels were quantified by real-time polymerase chain reaction using a standard curve formed after cloning each cytokine gene and a reference gene using recombinant DNA technology in a specific plasmid vector. In the patients group, mRNA expression of IFN-gamma, IL-2 and IL-4 but not IL-10 was detected, IFN-gamma being the predominant cytokine expressed. All four cytokines were expressed in subjects with self limited disease, however levels of IFN-gamma were lower and a significant higher expression of IL-10 compared to patients was found. There was a significant correlation between IFN-gamma mRNA expression levels and stage of fibrosis. Our findings show that in chronic hepatitis C, TH1 cytokines predominate and correlate to liver immunopathology. Furthermore, subjects with self-limited disease, maintain the ability to respond to HCV antigens for a long time after disease resolution.

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Lack of evidence for the Th2 predominance in patients with chronic hepatitis C

Cited by 14 publications

References 48 publications

Lymphocyte subset characterization associated with persistent hepatitis C virus infection and subsequent progression of liver fibrosis

Lymphocyte subset characterization associated with persistent hepatitis C virus infection and subsequent progression of liver fibrosis

Immunomodulatory Activities of IFN-γ1b in Combination with Type I IFN: Implications for the Use of IFN-γ1b in the Treatment of Chronic HCV Infections

Cytokine mRNA expression in hepatitis C virus infection: TH1 predominance in patients with chronic hepatitis C and TH1–TH2 cytokine profile in subjects with self‐limited disease

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