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…

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

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…

Sulphoevernan, a polyanionic polysaccharide, and the narcissus lectin potently inhibit human immunodeficiency virus infection by binding to viral envelope protein.

Sulphoevernan is a sulphated alpha-1----3, 1----4 polyglucan (Mr 20,000) with a helical structure. This compound effectively inhibits both human immunodeficiency virus type 1 (HIV-1) and type 2 infection of cells in vitro at concentrations around 0.5 micrograms/ml. Moreover, the compound completely inhibits HIV-1-induced syncytium formation at a concentration of 1 microgram/ml. Competition experiments with 35S-labelled sulphoevernan revealed that the mannose-specific lectin from Narcissus pseudonarcissus prevented binding of sulphoevernan to HIV-1, whereas the antibody OKT4A did not reduce the amount of sulphoevernan bound to MT-2 cells. These data indicate that the non-cytotoxic polymer su…

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…

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…