Hepatitis C virus antibody secretion in vitro by peripheral blood lymphocytes.

A recombinant polypeptide corresponding to a virus-specific cDNA clone (c100-3) serves as the antigen for a hepatitis C virus (HCV) antibody assay. Previous investigations have shown an 80% prevalence of HCV antibodies in sera of patients suffering from post-transfusional chronic hepatitis non-A, non-B, but positive results were also obtained for 30 to 70% of sera from patients with chronic hepatitis B or autoimmune hepatitis. In this study we show that HCV antibodies are secreted by peripheral blood lymphocytes (PBL) in vitro. PBL from 12/35 patients with chronic non-A, non-B hepatitis and 1/6 patients with chronic active hepatitis B spontaneously secreted HCV antibodies in cell culture su…

Modification of the immune response against hepatitis B virus by the human immunodeficiency virus.

Hepatitis B virus and the human immunodeficiency virus are similarly transmitted. Individuals with preexisting HIV infection have a higher chance to become HBsAg carriers than do anti-HIV negative persons. Cytotoxic T cells with specificity for HBcAg, that are under the control of HBcAg-specific helper T cells, are responsible for liver injury. There is good evidence that HIV infection lowers inflammatory activity, is associated with milder liver histology, high levels of viral replication and low seroconversion rates. In addition interferon alpha therapy is less effective in anti-HIV positive subjects. The immune response against HBsAg is helper T-cell dependent and vaccination against hep…

Human immunodeficiency virus infection mimics autoimmune hepatitis--a case report.

Autoantibodies against the human asialoglycoprotein receptor: Effects of therapy in autoimmune and virus-induced chronic active hepatitis

The hepatic asialoglycoprotein receptor (ASGPR) was recently identified as a target antigen for both humoral and cellular immune response in inflammatory liver diseases. Thereby anti-ASGPR autoantibodies directed against human substrate were closely associated with autoimmune chronic active hepatitis. The present study compares the occurrence, titer and immunoglobulin classification of anti-human(h-)-ASGPR antibodies in 23 patients with newly diagnosed autoimmune chronic hepatitis before and after initiation of immunosuppressive therapy to 22 patients with autoimmune hepatitis in remission. Additionally, 1-year follow-up examinations of 42 patients with HBsAg-positive chronic hepatitis and …

Ultrastructural localization of interferon-producing cells in the livers of patients with chronic hepatitis B

Cells expressing alpha- and gamma-interferon were localized in the liver tissue of patients with chronic hepatitis B by means of light and electron microscopy using monoclonal antibodies. Interferon-positive cells were regularly seen in the infiltrating mononuclear cells, and the number showed a good correlation with the degree of the necroinflammatory activity of the disease. In chronic persistent hepatitis and in normal livers, they were infrequent or virtually absent. alpha-Interferon was shown to be positive in lymphocytes, polymorphonuclear leukocytes and fibroblasts, Kupffer cells and, weakly, in the cytoplasm of a few hepatocytes in cases of active hepatitis, whereas gamma-interferon…

Natural killer cell activity as a prognostic parameter in the progression to AIDS.

Cost effectiveness of peginterferon α-2b plus ribavirin versus interferon α-2b plus ribavirin for initial treatment of chronic hepatitis C

Background: Peginterferon α-2b plus ribavirin therapy in previously untreated patients with chronic hepatitis C yields the highest sustained virological response rates of any treatment strategy but is expensive. Aims: To estimate the cost effectiveness of treatment with peginterferon α-2b plus ribavirin compared with interferon α-2b plus ribavirin for initial treatment of patients with chronic hepatitis C. Methods: Individual patient level data from a randomised clinical trial with peginterferon plus ribavirin were applied to a previously published and validated Markov model to project lifelong clinical outcomes. Quality of life and economic estimates were based on German patient data. We u…

Treatment of chronic type B hepatitis with recombinant alpha-interferon induces autoantibodies not specific for autoimmune chronic hepatitis.

Recombinant human alpha-interferon is now under intensive investigation as therapy for chronic Type B hepatitis. Recent reports have suggested that prolonged alpha-interferon therapy may induce autoimmune reactions. We have evaluated the problem of autoimmunity related to alpha-interferon therapy by testing for 15 different antibodies in the sera of 31 patients treated with alpha-interferon. No patient had autoantibodies before treatment; 27 (87%) of 31 patients developed at least one autoantibody. Eleven patients had antinuclear antibodies and 21 had smooth muscle antibodies, both of which usually developed during alpha-interferon therapy. In contrast, antibodies to endocrine organs such a…

Corynebacterium parvum (Propionibacterium acnes): an inducer of tumor necrosis factor-alpha in human peripheral blood mononuclear cells and monocytes in vitro.

The present study investigates the potential capacity of the immunostimulant Corynebacterium parvum (C.p.) to induce tumor necrosis factor-alpha (TNF-alpha) in human peripheral blood mononuclear cells (PBMC) and blood monocytes (BMo) in vitro. Both at the mRNA and protein level, stimulation of PBMC and BMo upon C.p. induces TNF-alpha. Compared to the hitherto used TNF-alpha inducers in vitro such as Sendai virus, phytohemagglutinin or lipopolysaccharide the C.p. stimulus displayed a threefold stronger induction of TNF-alpha production (p less than 0.001). Using C.p. as an inducer it was possible to demonstrate that TNF-alpha production is regulated by prostaglandin E2; preincubation of the …

Active immunization of homosexual men using a recombinant hepatitis B vaccine

Twenty homosexual men [13 anti-human immunodeficiency virus (HIV)-positive, seven anti-HIV negative] without HBsAg, anti-HBs, and anti-HBc were vaccinated with three 20 micrograms doses of a recombinant hepatitis B vaccine. All anti-HIV-positive homosexuals were nonresponders independent of the initial number of CD4-positive cells. Among seven anti-HIV-negative individuals, five responded. After three doses of the vaccine, CD4-positive cells fell in anti-HIV positive individuals by 22.4%. A similar fall in CD4-positive cells of an average 24.9% was noted in 17 matching, but nonvaccinated, anti-HIV-positive homosexuals. The study indicates that the efficacy of vaccination in anti-HIV-positiv…

Failure of acyclovir to enhance the antiviral effect of α lymphoblastoid interferon on HBe-seroconversion in chronic hepatitis B

Serum HBeAg levels and HBe-seroconversion were investigated in patients with chronic HBeAg-positive hepatitis who were randomized to receive either alpha lymphoblastoid interferon (5 megaunits subcutaneously daily for 16 weeks) plus acyclovir (2 g intravenously daily during weeks 1 and 2 and weeks 9 and 10) (n = 49) or no treatment (n = 48). HBeAg levels in serial dilutions of patient serum were assessed quantitatively by radioimmunoassay and compared with the values found for negative control serum. One year after the start of therapy 44 treated patients and 43 control patients were available for follow-up. A complete response (HBe-seroconversion) occurred in 11 treated patients (25%) and …

Tumornekrosefaktor und Interferon als prognostische Marker der HIV-Infektion

Peripheral blood cells were obtained from patients at different stages of their human immunodeficiency virus (HIV) infection. It was found that the capacity to generate interferon alpha was reduced already at Walter Reed stage 2 (WR) while the interferon gamma capacity remained largely unaffected until WR stage 4. Endogenous tumor necrosis factor (TNF) alpha production increased as the HIV disease progressed. The data obtained add to our knowledge on destruction of the immune system by the HIV. Moreover TNF and acid labile interferon alpha might contribute to HIV replication and disease progression. Nevertheless the tests performed are too time-consuming to be introduced into routine analys…

In Vivo Protective Effect of Tumour Necrosis Factor   Against Experimental Infection with Herpes Simplex Virus Type 1

C57BL/6 mice, which differ genetically from other strains by their resistance to herpes simplex virus type 1 (HSV-1) infection, were inoculated intraperitoneally with different doses of tumour necrosis factor alpha (TNF-alpha). Mice pretreated with 100 ng, or even 10 ng, of TNF-alpha showed prolonged survival compared to control mice that were infected with 10(7) p.f.u. of HSV-1. Significant protection was observed in mice injected 4 or 8 h prior to or after HSV-1 inoculation, respectively. Protection was also observed when mice which differed at their H-2 locus were treated with TNF-alpha after infection with HSV-1. Interferon could not be detected in the sera of mice at different time poi…

Treatment of Patients with Chronic Type B Hepatitis and Concurrent Human Immunodeficiency Virus Infection with a Combination of Interferon Alpha and Azidothymidine: A Pilot Study

Six patients with chronic type B hepatitis and concurrent infection with the immunodeficiency virus were treated with 600 mg azidothymidine (AZT)/day and 3 X 10(6) units of interferon-alpha (IFN-alpha) every other day for a total of 4 months. None of the patients treated lost the hepatitis B virus (HBV). HBV-DNA concentrations were not significantly influenced by this treatment. Human immunodeficiency virus (HIV) infection was also not affected except for a transient rise in CD 4-positive cells in 2 individuals, who had initially low CD 4-positive cells. Treatment did not influence the presence of HIV-Ag in the serum. In conclusion, a combination therapy of IFN and AZT does not seem to be b…

In vivo and in vitro induction of natural killer cells by cloned human tumor necrosis factor

The natural killer (NK) cell activity of mice in the peritoneal cavity is very low or undetectable and testing peritoneal NK cells is a useful model for studying the influence of activating substances upon local injection. Injection of tumor necrosis factor (TNF) at doses of 10-200 ng caused a marked activation of NK cell activity which was maximal after 24 h and declined rapidly on day 2. A similar effect was observed when interferons alpha and beta were injected, and there were additive results when interferon was injected together with TNF. The NK cell nature of the effector cells activated by TNF was substantiated by the finding that previous injection with anti-asialo GM 1 antibody pre…

Cytokine-mediated regulation of monocyte/macrophage cytotoxicity in human immunodeficiency virus-1 infection.

Monocyte/macrophage-mediated tumor cytotoxicity was studied in patients infected with human immunodeficiency virus-1 (HIV-1) at various stages [Center for disease control (CDC) classification] of the disease. using the P-815 tumor cell line as target cells, the results demonstrated reduced monocyte/macrophage cytotoxicity early in HIV-1-related disease (CDCIII, P0.01). This cellular dysfunction sustained during the progression of the disease. Evidence could be presented that neither exogenous application of macrophage-stimulating cytokines (e.g. interferons) nor their endogenous induction in vitro restored monocyte/macrophage cytotoxicity. However, enhanced tumor necrosis factor (TNF)-alpha…