Showing papers on "Interferon published in 1975"

Two antigenically distinct species of human interferon.

Abstract: Rabbit antisera prepared against interferon produced in human fibroblast cell cultures stimulated with poly(1).poly(C) neutralized the activity of interferon preparations produced in various human fibroblast cultures timulated either with poly(1)poly)C) or with viruses. However, these antisera showed no detectable neutralizing activity against interferon produced in cultures of human leukocytes. On the other hand, most rabbit antisera against the human leukocyte interferon were active in neutralizing both homologous interferon and fibroblast interferons. A preparation of antiserum against leukocyte interferon, active against both leukocyte and fibroblast interferons, was shown by affinity chromatography to have two distinct antibody populations, one of which was specific for the fibroblast interferon. We conclude that the heterologous neutralizing activity of sera from rabbits immunized with leukocyte interferon is liekly to be due to the presence of two antigenic species of interferon. The major antigenic species of leukocyte interferon preparations (designated "Le") is distinct from huamn fibroblast interferon. The minor species of leukocyte interferon ("F") is either identical with, or closely related to, interferon produced in human fibroblast cultures.

Sensitivity of the Epstein-Barr virus transformed human lymphoid cell lines to interferon.

Abstract: Summary 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.

A microplaque reduction assay for human and mouse interferon.

Abstract: A microplaque reduction assay for human and mouse interferons is described, using plastic disposable multicompartmental plates with flat-bottomed wells of 6 mm in diameter. The procedure is rapid a...

Characteristics of immune interferon produced by human lymphocyte cultures compared to other human interferons.

Abstract: A factor with antiviral activity has been produced in vitro by combined macrophage-lymphocyte cultures from patients with recent herpes labialis in response to HSV antigen stimulation. It has been designated “immune interferon” and characterized in comparison to several other human interferons. It was shown to be relatively unstable at pH 2 and at 56° C. Rabbit anti-human leukocyte interferon serum was shown to be less active against immune interferon than against diploid cell interferon or against vesicle fluid interferon. The possibility of immune interferon being a totally different anti-viral protein or a protein with certain shared antigen determinants or structures with classical viral interferon is discussed. A simplified method for the assay of anti-interferon sera with microtiter plates is also described.

Effects of Intravenous Silica on Immune and Non-Immune Functions of the Murine Host

Abstract: Silica, an agent toxic for macrophages, administered i.v. to DBA/2 mice rapidly depresses the clearance of colloidal carbon by the reticuloendothelial system and reduces the in vitro phagocytic activity of peritoneal macrophages harvested 3 days after silica injection. Silica blocks the humoral immune response to sheep erythrocytes and the cell-mediated immune response to allogeneic fibroblasts when given before antigen. Silica also induces complex alterations in spleen cell responsiveness to concanavalin A involving both local and serum factors. Silica had no significant effect on the induction of interferon by statolon or Newcastle disease virus. No unequivocal evidence was obtained that silica has a direct depressive effect on cells other than macrophages, but indirect effects on lymphocytes were produced most likely by factors released from silica-lysed macrophages. Intravenous silica may prove useful for the separation of interferon induction and immune response stimulation in studies of host resistance to infection and oncogenesis. Considerable variation exists in the immunodepressive effects of different preparations of silica.

Production of Human Lymphoblastoid Interferon

Abstract: The interferon response of 21 lines of human lymphoblasts varied greatly. Interferon from the best producer (11,000 U/ml) resembled human leukocyte interferon.

Lethality of interferon preparations for newborn mice.

Abstract: WE have previously reported that the daily subcutaneous inoculation of newborn mice with mouse brain interferon preparations was not accompanied by any discernible effect on their growth or development1. Far more potent interferon preparations have been shown to inhibit cell division in normal adult mice. Thus, the multiplication of allogeneic spleen and syngeneic bone marrow cells was inhibited when injected into X-irradiated adult mice treated for several days with potent interferon preparations2, and liver regeneration was inhibited in partially hepatectomised adult mice treated with interferon3. We report here that daily injection of potent interferon preparations results in the death of newborn mice. To our knowledge this is the first report of untoward effects associated with interferon treatment of the normal animal. These results may be relevant to the use of interferon in man.

Inhibition of the primary in vitro antibody response by interferon preparations.

Abstract: The primary in vitro plaque forming cell (PFC) response of mouse (C57BL/6J) spleen cells to sheep red blood cells (SRBC) was inhibited by two sources of crude and two sources of partially purified mouse interferon. The substance(s) in the interferon preparations which induced PFC and antiviral inhibitory activity have the following common characteristics: a) The interferon preparations were of different potencies and specific activities, but they inhibited the PFC response in proportion to their activities; 20 to 60 units were the minimal amounts required for τ;90% inhibition of the PFC response. b) Both the antiviral activity and the PFC inhibitory activity of the interferons were neutralized by antibody specific for mouse interferon. c) Both activities were partially or completely inactivated by heating at 60°C for 1 h. d) Human interferons had neither antiviral activity nor PFC inhibitory activity in mouse cells. e) Limited exposure (4 h) of cells to interferon significantly inhibits both viral infection and the PFC response. f) Both the antiviral activity and the PFC inhibitory activity of the interferon preparations are acid stable. It is concluded, therefore, that the inhibition of the primary in vitro PFC response is due to interferon in the preparations. Maximum inhibition of the PFC response occurred when interferon was added to cultures at the same time as SRBC. Significant inhibition was also observed when interferon was added 1 day later, and slight enhancement was observed when added at days 2 and 3 of SRBC addition. Kinetic data showed that the greater the concentration of interferon added to the cultures, the earlier the effect on the PFC response. The presence of interferon in cultures for the first 4 h is sufficient to inhibit the PFC response. Interferon, then, appears to affect some early event(s), which leads to inhibition of the PFC response. Since mature T cells can be one of the sources of interferon, we have demonstrated a suppressor effect of a T cell lymphokine. The precise relationship of interferon to various expressions of suppressor T cell effects remains to be determined.

Inhibition by interferon of delayed-type hypersensitivity in the mouse.

Abstract: The effect of interferon on delayed-type by persensitivity to picryl chloride and sheep erythrocytes was examined in the mouse. When administered to sensitized animals on the day before or the day of challenge, tissue culture interferon inhibited both the ear swelling induced by pieryl chloride and footpad swelling induced by sheep erythrocytes. Newcastle disease virus, when injected into sensitized If-1l or If-1h congenic mice a few hours before challenge, caused an inhibition of delayed-type hypersensitivity which could be related to the amount of serum interferon induced by the virus. These results indicate that interferon production may represent one of the factors responsible for the depression of cell-mediated immune reactions during virus infection.

Mechanism of the suppressive effect of interferon on antibody synthesis in vivo.

Abstract: Mouse interferon preparations significantly suppress the in vivo antibody response to sheep red blood cells (SRBC), a thymus-dependent antigen, and to Salmonella typhimurium lipopolysaccharide (LPS), a thymus-independent antigen. It is also possible to effect the late responses of antigen sensitive “memory” cells observed during secondary immunization by administration of interferon prior to primary immunization. The immunosuppressive activity of interferon was time- and dose-dependent. Maximum suppression was produced when animals were given 1.5 × 10 5 units of interferon between 4 and 48 hr before antigenic stimulation. These findings suggested that interferon affects some early event(s) in the process of antibody synthesis which might be related to the general inhibitory effect of interferon on rapidly dividing cells and viral m -RNA translation. In addition, the use of nonadherent spleen cell cultures from interferontreated mice, immunized in vitro with a thymus-independent antigen, indicated that in this situation the inhibitory effect of interferon was due to an action on B lymphocytes. A variety of soluble “suppressive” factors are secreted by T cells as a consequence of activation by mitogens or specific antigens in vitro. Since T cells are recognized as one of the sources of interferon, it is suggested that interferon should be investigated as a suppressor T cell-produced lymphokine which can regulate B cell expression.

Interferon-directed inhibition of chronic murine leukemia virus production in cell cultures: lack of effect on intracellular viral markers.

Abstract: Extracellular murine leukemia virus (MLV) reverse transcriptase activity was decreased by interferon treatment in four interferon-sensitive mouse cell lines which were chronic MLV producers. In three cell lines which were relatively insensitive to interferon, extracellular enzyme activity remained unchanged by interferon treatment. The concentrations of interferon used had no effect on DNA synthesis or cell replication of AKR,C+ cells which were chronic producers of AKR-MLV. In AKR,C+ cultures interferon treatment also had no effect on the level of intracellular viral reverse transcriptase activity in spite of an inhibition of extracellular enzyme activity. Treatment of AKRC+ cultures with interferon for 9 days inhibited extracellular viral reverse transcriptase levels throughout the period of treatment; however, the intracellular enzyme activity remained unchanged, and concentrations of viral p30 (gs) antigen were increased in the interferon-treated cells. When the cells were washed to remove interferon, however, virus production rapidly rose and intracellular p30 antigen fell to the levels of untreated AKR,C+ cells. These and previously reported results suggested that in interferon-treated AKR,C+ cells virus production is inhibited at a late step in the MLV replication cycle, either directly or through the inhibition of the production of a protein required for virus assembly.

Interferon crosses blood-cerebrospinal fluid barrier in monkeys.

Abstract: SummaryInterferon was detected in the cerebrospinal fluid (CSF) of monkeys injected iv or im with 30 million units of human leukocyte interferon. The im injection maintained a long-lasting plateau at about l/30th of the corresponding level of interferon in the serum. Interferon injected into the cerebrospinal canal was cleared from CSF at a similar rate as it disappeared from blood after iv administration of a high dose. A relatively stable serum level was maintained for 12-24 hr after the injection of interferon into the CSF space.

Affinity Chromatography of Human Leukocyte and Diploid Cell Interferons on Sepharose-Bound Antibodies

Abstract: Interferons produced in human peripheral leukocytes (LE) and foreskin fibroblast (FS-4) cells were subjected to affinity chromatography on Sepharose-bound globulins from rabbits immunized with these interferons Anti-LE interferon sera neutralized both interferons, but titers against FS-4 interferon were consistently lower than those against LE interferon Anti-FS-4 interferon sera neutralized only FS-4 but not LE interferon Accordingly, affinity columns constructed with anti-FS-4 globulin excluded LE but not FS-4 interferon, whereas those prepared with anti-LE interferon globulin bound and eluted both LE and FS-4 interferons Purification of native interferons of both types on anti-LE interferon-Sepharose ranged from 680- to 3,600-fold and recoveries from 72 to 126% Specific activities of eluate pools varied from 4 to 30 × 10 6 reference (B, 69/19) units per milligram protein

Immune specific production of interferon by human T cells in combined macrophage-lymphocyte cultures in response to Herpes simplex antigen.

Abstract: Human peripheral blood lymphocytes, highly enriched for T cells, were obtained by passing gravity-sedimented leukocytes through nylon wool columns. The eluted cells were cultured with autologous macrophages and the mixture was studied for its capacity to produce interferon in vitro in response to stimulation with herpes simplex virus antigen. The interferon produced by the combined macrophage-lymphocyte cultures was shown to depend upon the presence of T cells; elimination of these cells by treatment with an anti-T cell serum plus complement greatly diminished the amount of interferon produced. The memory for the immune-specific release of interferon also appeared to be carried by the T lymphocytes rather than the glass-adherent macrophages. Furthermore, the results suggest that under our conditions of culture immune-specific interferon originates from T cells.

Cyclic AMP potentiation of interferon antiviral activity and effect of interferon on cellular cyclic AMP levels.

Abstract: Summary Treatment of L cells with 3 to 10 mm 3′:5′-cyclic adenosine monophosphate (cAMP) in the presence of interferon was found to potentiate the development of antiviral activity. The dose response of interferon activity at various time periods in the presence and absence of cAMP indicated that potentiation of interferon activity by cAMP occurred at an early stage in the development of antiviral activity. Among the analogues of cAMP tested for interferon-potentiating activity, only the acylated derivatives were found to be active. Combined l-epinephrine and theophylline treatment of cells elevated cellular cAMP levels and also potentiated interferon-mediated antiviral activity. Interferon was also found to elevate cAMP levels in L cells. This activity was limited to biologically active interferon and antagonized the depression of cAMP associated with vesicular stomatitis virus (VSV) infection of L cells. These observations suggest that some aspects of interferon's biological activity is associated with an alteration in cellular levels of cAMP.

Human interferon therapy for herpes zoster in adults.

Abstract: Of 37 patients with herpes zoster 28 were treated with human exogenous interferon and 9 received only culture medium. The interferon was produced in leukocyte cultures and was given intramuscularly in one daily dose of 1 million units for 5–8 days. In the interferon-treated patients interferon was detectable in serum (peak level 1–5 hours after interferon injections) and in vesicle fluid, and in some patients also in urine samples. Anti-interferon antibodies were not found. Of the 28 interferon-treated patients 8 had a slight temperature increase and 4 showed a transient local reaction. In the interferon treated group of patients the duration of pain was shortened and the development of crust formation was enhanced compared with the control group.

Molecular structure of human fibroblast and leukocyte interferons: probe by lectin and hydrophobic chromatography.

Abstract: Structural differences between human leukocyte virus-induced interferon and human fibroblast polyinosinic-polycytidylic acid (rIn-rCn)-induced interferon have been noted in previous studies. This study reports the behavior of human leukocyte and fibroblast interferon, induced by virus and by rIn-rCn, in several lectin and hydrophobic chromatographic systems. Differences in both glycosylation and in hydrophobicity of human leukocyte and fibroblast interferons are documented. Human fibroblast interferon is a glycoprotein, whereas our evidence suggests that human leukocyte interferon probably is not. Also, fibroblast interferon is more hydrophobic than leukocyte interferon, as probed on several hydrophobic adsorbents. The possible relationships of these differences to each other and to antigenic variations are discussed. Generally, the differences appear to be attributable to the cell type in which the interferon was induced. However, our results suggest that at least subtle differences in the processing of the induction signal (virus or rIn-rCn) within the same cell type may occur, slightly altering some structural features.

Circulating Interferon in Man After Administration of Exogenous Human Leukocyte Interferon

Abstract: Interferon was measured at different intervals after the iv, sc, and im application of exogenous human leukocyte interferon to patients with various virus diseases or neoplasms. Interferon injected iv into patients had a half-life of about 15 minutes in the 1st hour and of about 90 minutes in the next 3 hours. Six hours after iv injection of 30 million U, no serum interferon was detectable. With a continuous iv infusion, a relatively high serum interferon level was reached. By the im administration of 1 million U interferon, a peak level of serum interferon (mean value 107 U/ml serum) occurred after 2 hours and was fairly stable for about 6 hours. Twenty-four hours after im application, a low level of serum interferon was still detectable. Similar results were found after sc interferon injections. In a patient with subacute sclerosing panencephalitis, no interferon was found in the cerebrospinal fluid at the time of the highest serum interferon level and 24 hours after two im interferon injections. Only minimal side reactions resulted from sc and im interferon injections. In one patient, a shock reaction occurred after iv application. For therapeutic trials, about 1 million U exogenous human interferon should be injected twice daily im or sc.

Enhancement of interferon production by poly(rI)-poly(rC) in mouse cell cultures by ascorbic acid.

Abstract: WE have reported1 an increased response to interferon induction in mice fed a diet containing vitamin C, and have now found a similar phenomenon in vitro. Addition of L-ascorbate to cultures of mouse cells (transformed L cells and normal embryonic fibroblasts) stimulated with polyinosinic acid · polycytidylic acid (poly(rI)·poly(rC)) resulted in increased synthesis of interferon.

Phagocytosis-enhancing effect of human leukocyte interferon preparation of human peripheral monocytes in vitro.

Abstract: It was found that the phagocytosis of human peripheral monocytes was enhanced by human leukocyte interferon preparations. This activity showed species-specificity and a positive correlation between interferon titer and phagocytic activity. When human monocytes were treated by interferon, the pahagocytic activity was enhanced. But when interferon was added to the latex, the enhancement was not observed. The interferon preparation did not only increase the number of phagocytic cells, but also enhanced the degree of phagocytosis in individual cells. The factor responsible for the enhancing effect was inactivated by trypsin, but was not inhibited by actinomycin D.

Delayed-type hypersensitivity to sheep red blood cells: inhibition of sensitization by interferon.

Abstract: Interferon, when given or induced 24 hours before contact of mice with sheep red blood cells, prevented sensitization, and no delayed-type hypersensitivity reaction could be elicited 4 days later, after challenge with the antigen, as shown by the absence of footpad swelling in treated animals.

Multiple active sites on human interferons

Abstract: Human interferons stimulated in peripheral leukocytes and foreskin fibroblasts are active in cultures of human and rabbit cells. The dominant factors in leukocyte and fibroblast interferons responsible for antiviral activity in rabbit cells were shown to be antigenically distinct from each other as well as from rabbit interferon. In addition, leukocyte interferon contained also a minor component with antigenic determinants characteristic of fibroblast specificity, which could be isolated by affinity chromatography on Sepharose-bound antibodies directed against firboblast interferon. Neutralization tests with selected anti-interferon sera suggested that the antiviral activities of leukocyte and fibroblast interferons in human and rabbit cells were associated with single molecules. A model is proposed where molecules of human interferon contain multiple reactive sites each of which is capable of interaction with cells of a different species. The number and distribution of these determinant sites may vary with the source of the human interferon and account for the differential in antiviral protection expressed in homologous and phylogenetically unrelated host cells.

Cellular events in zoster vesicles: relation to clinical course and immune parameters.

Abstract: The cellular responses in zoster vesicles was studied chronologically in 30 patients, some of whom were compromised hosts with disseminated disease. Cell counts were low initially but rose abuptly later. Polymorphonuclear leukocytes predominated at all times in the vesicular fluid and in the cells adherent to the vesicle base. The abrupt rise in the number of cells generally coincided with an abrupt rise in the titer of vesicular interferon; both increases preceded resolution of local infection and cessation of cutaneous dissemination in disseminated disease, but the sequence of the increases was variable. The peak interferon titer correlated with cessation of dissemination better than did peak cell counts, and the timing of the local events contrasted with appearance of complement-fixing antibody, which commonly occurred after the resolution of disease. Possible interpretations are that a few sensitized lymphocytes may initiate the defensive response, produce interferon, and/or produce chemotactic factors that augment the polymorphonuclear response. The appearance of polymorphonuclear cells may be a nonspecific inflammatory response, or these cells or the deeper mononuclear infiltrate seen in biopsies may contribute to the rise in local interferon.

Human interferon production: superinduction by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole

Abstract: Polyinosinic.polycytidylic acid [poly(I.C)] induced production of interferon by a strain of diploid human fibroblasts (FS-4), measured between 5 and 24 hours from induction, is enhanced up to 128-fold by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a reversible inhibitor of nuclear heterogeneous RNA synthesis. A normalized dose-effect plot shows a close correlation between the superinducing effect of DRB and inhibition of RNA synthesis. Cultures that contained DRB continue to produce interferon for up to 4 days. Removal of the drug at any time during this period leads to a prompt shutoff of interferon production.

Partial purification and characterization of RTG-2 fish cell interferon.

Abstract: Interferon produced by rainbow trout gonadal cells (RTG-2) was partially purified. The physical, chemical, and biological properties of this in vitro produced fish cell interferon were studied. Purification was achieved by ultracentrifugation, molecular sieve gel chromatography, ion exchange chromatography, and polyacrylamide gel electrophoresis. The isoelectric point of RTG-2 interferon, as determined by CM-Sephadex (C-50) chromatography, was 7.1. Filtration through Sephadex G-150 showed that RTG-2 interferon had a molecular weight of 94,000. The partially purified material was not sedimented at 105,000 times g for 2 h at 4 C. The fish cell interferon was non-dialyzable and exhibited heat and pH stability. The partially purified material was inactivated by treatment with trypsin or 2-mercaptoethanol, but was resistant to treatment with deoxyribonuclease or ribonuclease. RTG-2 interferon which was induced by infectious pancreatic necrosis virus exhibited antiviral activity against challenge with infectious hematopoietic necrosis virus or infectious pancreatic necrosis virus. Partially purified RTG-2 interferon exhibited greater species specificity than the crude material. Images