Antiviral effect of interferon in vivo may be mediated by the host.
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Biomedical subjects
Publications and source records attributed to H Schellekens.
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Six patients with hepatitis B surface antigen, hepatitis B 'e' antigen positive chronic active hepatitis, and elevated hepatitis B specific DNA polymerase activity were treated sequentially with fibroblast and leucocyte interferon. Fibroblast interferon induced a fall in serum transaminase activities in all patients, whereas a consistent decline in DNA polymerase activity was observed during leucocyte interferon administration only. After treatment one patient remained persistently DNA polymerase and hepatitis B 'e' antigen negative, whereas relapse to initial values occurred in others. Side effects included severe but reversible granulocytopenia, and chills responding to promethazine treatment. The differential biologies with their non-identity in in vitro studies.
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Different forms of prophylaxis and therapy of HBsAg positive hepatitis are discussed. Prevention of HBsAg positive hepatitis has been attempted by passive and active immunisation. For passive immunisation against parenteral infections hepatitis B immunoglobulin (HBIG) of high titer has to be used. However, the protection provided by HBIG is incomplete and temporary. Therefore active immunisation is to be preferred for protection of high risk groups. Experiments using the 22 nm spheric particles prepared from plasma of chronic carriers showed the efficacy of this type of vaccine. The direct way to treat the different forms of hepatitis B is the eradication of the virus from the body. Success has been claimed with the use of interferon and adenine arabinoside. However, this antiviral therapy is still in an experimental stage. In some forms of HBsAg positive hepatitis the liver damage is supposed to be the result of an immune response against the virus. Immunosuppression in these conditions failed, however, to show a beneficial effect. Corticosteroids turned out to be harmful in all forms of acute hepatitis and are therefore contraindicated. Chronic hepatitis B seems to be caused by the inability of the immune system to clear the virus. Successful results have been claimed employing immune stimulative agents like BCG, levamisole, and transfer factor. Most of these reports, however, are anecdotycal and the more comprehensive studies are uncontrolled.
In a double-blind trial renal allograft recipients were treated with fibroblast interferon preparations for 3 months in an attempt to prevent viral infections. Interferon therapy did not reduce the overall incidence of viral infections. No adverse effects were noted on liver function, platelet counts, or leucocyte counts, or acute rejection episodes.
The toxicity of interferon to bone marrow was studied by the use of in vitro colony forming assays for hemopoietic cells. In the same study the relative inhibitory effects of two clinically common interferon preparations, leukocyte and fibroblast interferons, were compared with regard to their effect on both myeloid [colony-forming unit, culture (CFUc)] and erythroid [colony-forming unit, erythroid (CFUe)] progenitor cells. CFUe formation in human bone marrow cells in vitro appeared to be fairly resistant to both interferons. Only high doses of both interferons gave a marked inhibition of CFUe. However, the toxicity of leukocyte and fibroblast interferon was divergent for CFUe in human bone marrow. Leukocyte interferon appeared to be considerably more inhibitory for CFUe than was fibroblast interferon. The effects of mouse interferon, induced in L929 cells, on the growth of CFUc and CFUe in murine bone marrow cells were comparable with those of fibroblast interferon on human cells. The toxicity of human and murine interferon was species specific. Except for the toxicity of leukocyte interferon to CFUc in human bone marrow, the toxicity of interferon was marked only with concentrations on interferon far exceeding the amount necessary to produce an antiviral state in vitro.
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The effect of interferon on the replication of vesicular stomatitis virus (VSV) and type-C oncornavirus in two Balb/c mouse cell lines, JLS-V5 and JLS-V9R, infected with MuLV-R was examined. VSV replication was inhibited threefold (0-5 log10) in both cell lines by 10 to 20 units of interferon/ml. In JLS-V5 cells C-type virus yields, as measured by 3H-uridine incorporation and reverse transcriptase activity, were also reduced threefold by 10 to 20 units of interferon/ml. However, in JLS-V9R cells, C-type virus replication was refractory to interferon at concentrations up to 1 x 10(4) units/ml. Infectious C-type virus transmitted from JLS-V9R cells to Balb/3TS cells was as sensitive to interferon as virus transmitted from JLS-V5 cells, indicating that resistance of C-type virus in JLS-V9R cells is a feature of the cells rather than of the virus strain.