Production of cytokines in patients infected by hepatitis C virus.

INSERM U 74, Strasbourg, France.
Journal of Medical Virology (Impact Factor: 2.37). 07/1998; 55(2):89-91. DOI: 10.1002/(SICI)1096-9071(199806)55:23.0.CO;2-J
Source: PubMed

ABSTRACT T helper type 1 (Th1) cytokines play an important role in antiviral defence. The purpose of this study was to quantify by ELISA IL2, soluble receptor of IL2 (IL2Rs), IFNgamma TNFbeta, IL4, IL6 and IL10 levels in the sera of 134 HCV-positive patients, 69 of whom were coinfected with HIV, and in 54 HIV-HCV-negative patients. The mean IL2Rs and IFN serum levels were much higher in patients with anti-HCV than in the control group, whereas the mean IL4 and IL6 levels were lower in patients infected with HCV. There were no significant differences in cytokine levels between patients with and without HIV. There were significantly less patients with HCV than controls with IFNgamma levels under cut-off, and significantly more patients with HCV with IL4 levels under cut-off. Although serum level of cytokines must be interpreted with caution, the results suggest that Th1 response is enhanced in HCV infection.

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    ABSTRACT: Recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT) is nearly universal. Cytokines play an important role in the immune response to viral infection, and cytokine gene polymorphism affects the overall expression and secretion of cytokines. The objective of this study was to define the relationship between cytokine polymorphism and recurrent hepatitis C after OLT. Blood samples were collected from 36 patients at a mean of 44.6+/-30.4 months after OLT for chronic HCV infection. DNA was extracted from peripheral blood mononuclear cells, and polymerase chain reaction-sequence specific primers (PCR-SSP) analysis was performed on promoter sequences of transforming growth factor beta1 (TGF-beta1), interleukin 6 (IL-6) interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (INF-gamma). Liver biopsies performed at diagnosis of recurrent disease were graded with the Knodell score, and hepatic TGF-beta1 expression was determined semiquantitatively by immunohistochemistry. The gene polymorphism of TGF-beta1 was correlated with its expression on hepatocytes and sinusoids. Polymorphism in all studied cytokine genes was correlated with recurrence, and interval to recurrence (>12 or < or =12 months post-OLT), and clinical (ascites, Child-Pugh score and death), biochemical parameters of recurrent HCV (serum alanine aminotransferase (ALT)), INR, albumin, bilirubin), and virological parameters (HCV genotype and load). Biopsies revealed recurrent HCV in 31 patients (86.1%); in 21 (67.7%), the interval to recurrence was 12 months. There was a statistically significant correlation between TGF-beta1 gene polymorphism, i.e., the genetic ability to produce high levels of TGF-beta1, and the intensity of TGF-beta1 staining on hepatocytes (p=0.003) and sinusoids (p=0.003), and the degree of fibrosis (p=0.02). A borderline correlation was found with the presence of ascites (p=0.007), but not with Child-Pugh score, synthetic liver function tests or HCV genotype and load. The genetic ability to produce low levels of IFN-gamma was correlated with recurrent disease (p=0.015). No such correlation was found for TGF-beta1 gene polymorphism. In conclusion, polymorphism in the TGF-beta1 gene correlates with its in situ hepatic expression in patients with recurrent HCV after liver transplantation. INF-gamma, but not TGF-beta1 gene polymorphism, correlates with early recurrent hepatitis C after transplantation. These findings might help to design preemptive prevention therapy in selected patients at risk.
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