Stressor exposure and immunological response in man: interferon-producing capacity and phagocytosis.
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Biomedical subjects
Publications and source records attributed to H Strander.
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The incidence of acute infections in eight patients with osteosarcoma who are receiving interferon regularly is currently being compared with the incidence among their family members. Observations thus far indicate that the patients treated with interferon are less frequently and less severely ill than their untreated family contacts. The study is continuing, and the patients will also be observed after discontinuation of interferon treatment. Sera are regularly frozen for future viral serologic tests. The preliminary clinical data indicate that therapy with exogenous interferon may afford protection against common acute infections.
The treatment of a case of Hodgkin's disease (lymphocyte predominance, stage IV B) with exogenous i.m. interferon therapy is described. B symptoms disappeared, diseased nodes and pulmonary infiltrations decreased in size, and laboratory values normalized. Clinical improvement was associated with increased mitogenic responsiveness of the patient's lymphocytes towards various stimuli in vitro. After almost half a year's treatment tumour progression and a decreased mitogenic response were again observed. Interferon treatment was then abandoned and combined cytostatic courses were instituted. Partial remission was achieved after 6 months of cytostatic therapy, i.e. 1 year after the start of treatment.
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The effect of interferon on expression of Epstein-Barr virus (EBV) early gene functions was investigated. The 'early antigen' synthesis which follows either EBV superinfection of established lymphoid cell lines or 5'-iododeoxyuridine activation of the intrinsic EBV genomes harboured by these cells could be suppressed with interferon. In contrast, the spontaneous early antigen expression that occurs in a few per cent of the cells in the producer cell lines could not be blocked with interferon. The lymphoid cell lines tested differed in their ability to acquire an antiviral state after exposure to interferon. Several cell lines were also growth inhibited by the interferon preparations. The antiviral and growth inhibitory activities of different interferon preparations could not be separated by a number of criteria.
Established human lymphoid cell lines, many of which spontaneously produce interferon, differ in the efficiency by which they allow expression of Epstein-Barr virus (EBV) lytic functions. Six EBV carrying lymphoid cell lines, selected to either be extremely susceptible or very refractory to EBV superinfection, were tested for spontaneous interferon production. Only the three cell lines which were poorly superinfectable with EBV were found to produce interferon. These same three lines could not be induced to express EBV-specific early antigens from intrinsic EBV genomes. It is suggested that interferon acts as a negative control factor affecting a cell's susceptibility to EBV.
The interferon response of 21 lines of human lymphoblasts varied greatly. Interferon from the best producer (11,000 U/ml) resembled human leukocyte interferon.
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The recovery of interferon from Sendai-infected suspensions of purified human leukocytes is dependent on the serum concentration in the incubation medium. Very little interferon is obtained from serum-free suspensions. The data reported demonstrate that the critical macromolecular, age-independent, and species-unspecific serum principle can be omitted from the suspensions if the medium is supplemented with a combination of crystalline serum albumin and high concentrations of any one of five studied dipolar ionic buffers [N,N-bis(2-hydroxyethyl) glycine (Bicine), N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), 2-(N-morpholino)ethanesulfonic acid (MES), N-tris(hydroxymethyl)methyl-2-amino-ethanesulfonic acid (TES), and N-tris(hydroxymethyl)methylglycine (Tricine)]. The optimal combination [TES (1.0%, w/v) and bovine serum albumin (0.8%, w/v)] allows the production of potent preparations of serum-free human interferon.
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