BackgrounaYAims:Oxidative stress could play a role in the pathogenesis of hepatitis C virus infection. We investigated the oxidant/antioxidant status in peripheral blood mononuclear cells from patients with chronic hepatitis C and controls. Methods/Results: Lipid peroxidation products and superoxide dismutase activity in peripheral blood mononuclear cells were higher in chronic hepatitis C patients than in healthy subjects while glutathione Stransferase activity was reduced in patients as compared to controls. Catalase, glutathione peroxidase and glutathione reductase were similar in chronic hepatitis C and normal individuals. No statistically significant differences were found between patients and controls with regard to glutathione levels in peripheral blood mononuclear cells, but 35% of patients

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Viral infections stimulate the transcription of interferon type I, which includes IFN-alfa (IFN-␣) (13 subtypes) and IFN-␤ (a single substance). Hepatitis C virus (HCV) infection is remarkable by itsInterferon alfa (IFN-␣) and IFN-␤, two members of the type I IFN family, are produced by a great diversity of cells in response to viral infections. 1,2 Type I IFNs constitute the first line of defense against viruses by displaying direct antiviral effects and also by interacting with the cytokine cascade and the immune system, having regulatory effects on growth and differentiation of T cells. 3,4 While IFN-␤ is a glycoprotein product of a single gene, IFN-␣ is a family of 13 structurally related polypeptides (subtypes), each encoded by a separate gene. 5 Human IFN-␣ genes are expressed constitutively in organs of normal individuals, 6,7 and show restricted cell-type expression. 8 It has been shown that the antiviral activity and immunoregulatory properties differ among IFN-␣ subtypes. 9 However, tissue specificity and the biological role of the diverse IFN-␣ subtypes remain to be determined. In particular, little is known concerning the IFN-␣ subtypes expressed in normal and diseased livers.Viral infections activate transcription of type I IFN genes. 10 The promoters of IFN-␣ and IFN-␤ genes contain different response elements. 11 Functional differences between the promoters explain, at least in part, the tissue-specific expression patterns of the two IFN subfamilies. The specificity is achieved by the interaction of virus-induced cell-specific factors with regulatory domains in the promoters of IFN genes. 12,13 As in other chronic viral diseases, 14 the tendency of hepatitis C virus (HCV) infection to evolve to chronicity may depend not only on its ability to escape immunity, 15,16 but also on its capacity to deactivate the endogenous IFN system. In fact, in vitro studies have suggested that HCV may interfere with intracellular signaling of type I IFNs 17 ; however, there are no data in the literature on the possible effects of this virus on the transcriptional expression of IFN-␣ and -␤ in vivo. A main reason for this is technical problems, because mRNA of type I IFN is not abundant, and techniques based on cDNA amplification have the risk of amplifying genomic DNA along with cDNA as a result of the fact that type I IFN genes lack introns. In this work, we have analyzed the expression of IFN-␣ subtypes in samples of normal liver tissue obtained at laparotomy and in liver biopsies from patients with chronic hepatitis C. In addition, we have used a sensitive and specific polymerase chain reaction (PCR)-based technique to determine the levels of mRNA of IFN-␣ and -␤ in the liver and peripheral blood mononuclear cells (PBMC) in patients with chronic hepatitis C and controls to better understand the interaction of HCV with the endogenous IFN system. PATIENTS AND METHODSSamples of normal liver tissue were obtained from 11 patients (8 males and 3 females; age range, 49-70 years) who underwent laparotomy because of early...

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The aim of this study was to examine the levels of gamma interferon (IFN-␥)-, interleukin 4 (IL-4)-, and IL-8-producing cells in peripheral blood mononuclear cells from mink infected with the Aleutian mink disease parvovirus (ADV). As expected, ADV-infected mink developed high plasma gamma globulin values (hypergammaglobulinemia) and enhanced quantities of CD8-positive (CD8؉ ) cells in the blood during the infection. We quantified the percentages of IFN-␥-and IL-4-positive lymphocytes and IL-8-positive monocytes up to week 38 after virus challenge. The results clearly indicated marked increases in the percentages of IFN-␥-and IL-4-producing lymphocytes during ADV infection. The total number of IL-8-producing monocytes in the blood of ADV-infected mink stayed fairly constant during the infection. In order to characterize the phenotype of the cytokine-producing cells, we performed double-labeling fluorescence-activated cell sorter (FACS) experiments with CD8 surface labeling in one channel and cytokine intracellular staining in the other. We found that most IFN-␥ and IL-4 in ADV-infected mink was produced by CD8؉ cells, while in the uninfected mink, these cytokines were primarily produced by a cell type that was not CD8 (possibly CD4-positive cells). We also observed that IL-8 was almost exclusively produced by monocytes. All of the above findings led us to conclude that both Th1-and Th2-driven immune functions are found in mink plasmacytosis.Aleutian mink disease (AD), also known as mink plasmacytosis, is a common and economically important disease in mink. It is caused by a persistent infection with Aleutian mink disease virus (ADV), a nondefective parvovirus (16). In newborn mink, ADV infection may cause atypical interstitial pneumonia (10). This was observed just 20 years ago (34). The classical (adult) form of AD was described in 1956 by Hartsough and Gorham (30), and the disease is characterized by development of hypergammaglobulinemia (plasmacytosis), elevated levels of CD8-positive (CD8 ϩ ) lymphocytes, viral persistency, and immune complex formation (1,2,15,44). The most common pathological findings are glomerulonephritis and arteritis, and severely affected mink often die of renal failure (44). ADV cannot be neutralized in vivo despite the presence of very high concentrations in serum of antibody to virus capsid proteins (8,45). In fact, antibody-mediated enhancement of infection has been observed in connection with ADV infection (3,14,15,32,43). With regard to the identity of the in vivo ADV replicating cell(s) it is generally agreed that the virus-permissive cells probably are Fc receptor-positive cells (7,11,15,32).There is only one existing report on cytokine levels during ADV infection (15). Using reverse transcription-PCR technology, this study reported higher interleukin 6 (IL-6) mRNA levels in lymph nodes from ADV-infected mink (10 and 60 days after infection) than from uninfected mink. It also found biologically active IL-6 in supernatants from short-term lymph node cultures from ADV-infected mi...