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Migration Inhibitory Factor and Interferon in the Circulation of Mice with Delayed Hypersensitivity

Salvin, S. B.; Youngner, J. S.; Lederer, W. H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1973 Português
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When mice infected with Mycobacterium tuberculosis strain BCG were inoculated intravenously with old tuberculin (OT) or living BCG cells, both migration inhibitory factor (MIF) and interferon appeared in the circulation within a few hours. In such animals, which showed delayed hypersensitivity by footpad tests, as little as 1.5 mg of OT or as few as 1.7 × 106 bacteria per mouse were capable of eliciting circulating MIF and interferon. Uninfected animals inoculated with large doses of OT or living BCG cells did not produce MIF or interferon. When nonspecific stimuli such as bacterial lipopolysaccharide (LPS; from Salmonella typhimurium strain LT-2), heat-killed Brucella abortus, Newcastle disease virus (NDV), and polyinosinic acid:polycytidilic acid (poly I:C) were inoculated intravenously into BCG-infected mice, MIF was produced in the circulation of animals challenged with LPS or Brucella but not in those challenged with NDV or poly I:C, although all the stimuli were capable of eliciting an interferon response. The interferon elicited in BCG-infected mice by specific antigen differed in at least one important property from the viral inhibitor produced by the nonspecific stimuli. The interferon which appeared after injection of OT or living BCG cells was destroyed by treatment at pH 2 for 24 hr at 4C...

Interferon Messenger RNA: Translation in Heterologous Cells*

Maeyer-Guignard, Jaqueline De; Maeyer, Edward De; Montagnier, Luc
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1972 Português
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A viral inhibitor with the characteristics of mouse interferon is produced by avian and simian cells preincubated with RNA extracted from interferon-producing mouse cells. Similarly, RNA extracted from interferon-producing monkey cells induces a monkey interferon-like substance in avian cells and also in a line of simian cells, VERO, which normally lacks the capacity to produce its own interferon. In both cases, the RNA effect is inhibited by treatment of the receptor cells by cycloheximide, but not by actinomycin D. We conclude that interferon messenger RNA has been translated in the receptor cells. Thus, the production of interferon in heterologous cells can be used as a sensitive assay of interferon messenger RNA.

Relationship between interferon production and interferon messenger RNA synthesis in human fibroblasts.

Raj, N B; Pitha, P M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1977 Português
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Poly(A) containing mRNA prepared from poly(rI)-poly(rC)-induced human fibroblasts stimulated [14C]leucine incorporation into protein in wheat germ cell-free extracts. For the translation of interferon mRNA into a biologically active product, the presence of spermine was essential. The protein synthesized in vitro fulfilled the criteria for human interferon--namely, its antiviral activity was species specific, and its activity was completely neutralized by antiserum to human fibroblast interferon. The amount of interferon synthesized in human fibroblasts induced by poly(rI)-poly(rC) (normal induction) and poly(rI)-poly(rC) in the presence of cycloheximide (superinduction) was compared to the amount of translatable interferon mRNA both in the wheat germ cell-free system and the Xenopus oöcyte system. Although the production of interferon after the termination of transcription by actinomycin D was markedly increased in superinduced cells, the measurable amount of interferon mRNA as assayed in the oöcyte system was only slightly higher in superinduced cells than in cells induced with poly(rI)-poly(rC) alone. When compared in the wheat germ cell-free system, however, the translational product of mRNA preparation from cells induced with poly(rI)-poly(rC) alone was inactive while that from superinduced cells was active.

Induction and decay of human fibroblast interferon mRNA.

Cavalieri, R L; Havell, E A; Vilcek, J; Pestka, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1977 Português
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Polyadenylylated interferon mRNA, obtained from induced human fibroblasts, was quantitatively assayed by synthesis of biologically active human interferon in Xenopus laevis oocytes. The assay for interferon mRNA was used to distinguish between various hypotheses relating to interferon induction and biosynthesis. The data demonstrate that on induction with poly(I-poly(C) human fibroblasts accumulate interferon mRNA for 1-1.5 hr, after which time the mRNA is rapidly degraded with a half-life (t 1/2) of 18 min. Treatment of cells with cycloheximide prolongs the period of accumulation to 3 hr and decreases the rate of mRNA inactivation (t 1/2 = 49 min). Treatment with actinomycin D decreases the rate of inactivation still further (t 1/2 = 68 min). A comparison of cellular interferon synthesis with the relative amounts of interferon m RNA after simple induction or inductionin the presence of the inhibitors (superinduction) indicated a general correlation. Thus, on induction, the genes for interferon are activated to produce a transcript for a short time. The superinducing treatments prolong the period of accumulation and decrease the rate of degradation of this transcript.

Long-term follow up of patients with dilated heart muscle disease treated with human leucocytic interferon alpha or thymic hormones initial results.

Mirić, M.; Vasiljević, J.; Bojić, M.; Popović, Z.; Keserović, N.; Pesić, M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1996 Português
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OBJECTIVE: To determine whether giving interferon-alpha or thymomodulin in addition to conventional treatment improves cardiac function in patients with idiopathic myocarditis and idiopathic dilated cardiomyopathy. DESIGN: Single-centre, randomised, open label, parallel group comparison of conventional treatment plus interferon-alpha, conventional treatment plus thymomodulin, and conventional treatment alone. PATIENTS: 38 patients aged 19-54 years (23 men) with biopsy-proven myocarditis or dilated cardiomyopathy. 12 were treated with conventional treatment alone, 13 were treated with interferon-alpha and conventional treatment, and 13 with thymomodulin and conventional treatment. SETTING: Tertiary cardiac referral centre. MAIN OUTCOME MEASURES: Clinical evaluation, echocardiography, and Holter monitoring at baseline, 6 months, and 1 and 2 years. Radionuclide ventriculography at rest and during exercise after 2 years. Endomyocardial biopsy at baseline and after a year if the initial diagnosis was myocarditis. RESULTS: Left ventricular ejection fraction was improved in 21 (81%) of 26 patients after interferon-alpha or thymomodulin administration and in 8 (66%) of 12 conventionally treated patients (P < 0.05) at 2 year follow up. The maximum exercise time was significantly longer at 2-year follow up in patients treated with immunomodulators (mean (SEM) 5.1 (0.6) minutes for interferon-alpha and 5.0 (0.4) minutes for thymomodulin) than in conventionally treated patients (3.3 (0.4) minutes). Left ventricular ejection fraction during exercise (assessed by radionuclide ventriculography) improved in 9 of 12 patients treated with interferon-alpha...

Induction of Interferon and Erythropoietic Differentiation in Cells Transformed by Friend Virus

Swetly, P.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1976 Português
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Two lines of Friend virus (FV)-transformed mouse spleen cells have been analyzed in respect to their interferon production capacity: neither F4 cells, which liberate infectious FV when kept under tissue culture conditions, nor the thymidine kinase-deficient B8 cells, which do not produce significant amounts of FV, release detectable amounts of autogenous interferon into cell supernatants. However, interferon is produced in these cells in amounts comparable to that in L-929 cells when interferon induction is initiated with UV-inactivated Newcastle disease virus. Conversely poly(I) · poly(C), a potent interferon inducer in L-929 cells, proved ineffective in this capacity in F4 or B8 cells. When erythropoietic differentiation is induced in these cells by dimethyl sulfoxide, no autogenous interferon production occurs, but with NDV-induction a four- to fivefold increase of interferon production is observed. A similar elevation of interferon production is achieved during 5-bromodeoxyuridine stimulation of differentiation in the thymidine kinase-deficient B8 cells. The refractiveness against poly(I) · poly(C) displayed in unstimulated cells is not overcome at any stage of differentiation, indicating major differences of Newcastle disease virus and poly(I) · poly(C) induction mechanisms.

Production of Interferon in Mice: Effect of Altered Gaseous Environments

Huang, Kun-Yen; Gordon, Francis B.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1968 Português
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Effects of altered gaseous environments (parabarosis) on interferon production in mice were studied, with Newcastle disease virus (NDV) as the inducer. Increased levels of interferon in lung tissue were observed when mice were exposed to 11% O2 in N2 for 3 days before and after, or only after, injection of NDV. However, serum interferon levels remained unchanged. Exposure of mice to 77% O2 for up to 7 days did not affect the response to interferon induction as assayed in lungs or sera. Interferon levels were significantly depressed in mice exposed to a simulated depth of 213 ft in seawater [with normal partial pressure of O2 (pO2) in N2] for 2 or 4 weeks. Whereas definite depression of interferon was also observed in mice maintained at a simulated altitude of 37,000 ft (with normal pO2) for 2 weeks, those maintained at the same condition for 4 weeks showed a normal level of interferon. The results obtained with hypoxia are compatible with other reports on the influence of O2 tension on viral infection. The factors responsible for alterations observed in interferon level in mice kept in normal pO2, but under altered pressure, have not yet been identified.

Response of cloned progeny of clinical isolates of herpes simplex virus to human leukocyte interferon.

Lazar, R; Breinig, M K; Armstrong, J A; Ho, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1980 Português
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First- and third-generation cloned progeny viruses were derived from clinical isolates of herpes simplex virus and examined for their sensitivities to human interferon by inhibition of plaque formation in Vero cells. The dose-response curves obtained with the first- and third-generation clones were similar to those obtained with the parental isolates, and both the parent and the clones showed similar sensitivities to interferon. These results suggest that clinical isolates of herpes simplex virus consist of a homogeneous population of virus particles with respect to interferon sensitivity. The dose-response curves obtained with herpes simplex virus demonstrated a shallower slope than those obtained with vesicular stomatitis virus. Vesicular stomatitis virus plaque formation as completely inhibited at high concentrations of interferon, whereas complete inhibition of plaque formation by herpes simplex virus did not occur at the highest concentration of interferon used. Cloned progeny were derived from plaques appearing in the presence of high concentrations of interferon. The dose-response curves and interferon sensitivities of these clones were similar to those of the parent and third-generation clone from which they were derived. There was no evidence for genetic heterogeneity with respect to interferon sensitivity.

Effect of recombinant interferon alpha 2 on clinical course of first episode genital herpes infection and subsequent recurrences.

Mendelson, J; Clecner, B Y; Eiley, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1986 Português
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Herpes genitalis is an infection associated with considerable morbidity. Acyclovir, though effective, must be taken daily to prevent recurrences. The effects of interferon on this infection were therefore investigated. In a randomised double blind study, 31 patients with first episodes of genital herpes infection were studied to assess the effect of interferon on the presenting episode and on recurrences. Interferon (5 X 10(6) IU) was administered once daily subcutaneously during a five day "treatment" period followed by a three month "maintenance" period (1 X 10(6) IU three times weekly). Interferon had no effect on first episode herpetic attacks. During interferon administration women showed a trend towards reduced healing time and viral shedding in recurrences, but the differences were not significant and no effect was noted in women after administration of interferon. Interferon reduced assessed healing time and viral shedding in recurrences, however, in men (p = 0.05) during interferon administration, and this continued as a trend after treatment.

Interferon Alfacon-1 Protects Hamsters from Lethal Pichinde Virus Infection

Gowen, Brian B.; Barnard, Dale L.; Smee, Donald F.; Wong, Min-Hui; Pace, Anne M.; Jung, Kie-Hoon; Winslow, Scott G.; Bailey, Kevin W.; Blatt, Lawrence M.; Sidwell, Robert W.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /06/2005 Português
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Hemorrhagic fever of arenaviral origin is a frequently fatal infectious disease of considerable priority to the biodefense mission. Historically, the treatment of arenaviral infections with alpha interferons has not yielded favorable results. Here we present evidence that interferon alfacon-1, a nonnaturally occurring bioengineered alpha interferon approved for the treatment of chronic hepatitis C, is active against Pichinde and Tacaribe arenaviruses in cell culture. In the hamster model of Pichinde virus (PCV) infection, interferon alfacon-1 treatment significantly protected animals from death, prolonged the survival of those that eventually died, reduced virus titers, and limited liver damage characteristic of PCV-induced disease. Moreover, interferon alfacon-1 also demonstrated therapeutic activity, to a lesser degree, when the initiation of treatment was delayed up to 2 days post-virus challenge. Despite the observed advantages of interferon alfacon-1 therapy, efforts to stimulate the immune system with the known interferon inducer poly(I:C12U) (Ampligen) offered only limited protection against lethal PCV challenge. Taken together, these data suggest that the increased potency of the bio-optimized interferon alfacon-1 molecule may be critical to the observed antiviral effects. These data are the first report demonstrating efficacious treatment of acute arenaviral disease with alpha interferon therapy...

Interferon induction with polyinosinic:polycytidylic acid in the newborn piglet.

Loewen, K G; Derbyshire, J B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1986 Português
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Newborn piglets were treated with various doses of polyinosinic:polycytidylic acid intravenously and their serum interferon responses determined by a plaque reduction assay with vesicular stomatitis virus in Madin-Darby bovine kidney cells. A single dose of 5 mg of polyinosinic:polycytidylic acid was found consistently to induce detectable levels of interferon in serum, while the response to lower doses was inconsistent and higher doses produced clinical signs of toxicity. Piglets receiving 5 mg of polyinosinic:polycytidylic acid had maximum serum interferon titers between four and eight hours after treatment, and interferon was no longer detected at 72 hours after treatment. Following treatment with polyinosinic:polycytidylic acid leukopenia was observed, coincident with peak serum interferon titers. Elevated levels of serum glutamic oxaloacetic transaminase and blood urea, indicative of hepatic and renal dysfunction respectively, were also observed following interferon induction with polyinosinic:polycytidylic acid. Piglets treated with polyinosinic:polycytidylic acid also demonstrated antiviral activity in their intestinal mucosal tissues and intestinal washes, but the antiviral activity in the intestinal wash was not characterizable as interferon. A factor in the intestinal washes from newborn piglets was found to antagonize the antiviral effects of interferon by enhancing the plaque forming ability of vesicular stomatitis virus.

The interferon sensitivity of selected porcine viruses.

Derbyshire, J B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1989 Português
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The objective of this study was to compare the sensitivity of 11 porcine viruses to the antiviral effects of porcine interferon-alpha in serum from piglets which had been infected 19 h previously with transmissible gastroenteritis virus, and of porcine interferon-beta prepared in PK-15 cells by induction with polyinosinic:polycytidylic acid, in yield reduction assays in pig kidney cells which were treated with interferon before virus challenge, and both before and after virus challenge. The most sensitive virus to both types of interferon was vesicular stomatitis. A porcine isolate of bovine herpesvirus type 1, hemagglutinating encephalomyelitis virus and porcine enterovirus types 1 and 2 were also highly sensitive to interferon-alpha. There was little reduction in the yield of porcine parvovirus or porcine rotavirus, while swinepox, swine influenza and transmissible gastroenteritis viruses were intermediate in their sensitivity to interferon-alpha. In addition to vesicular stomatitis virus, porcine adenovirus type 3, swine influenza, hemagglutinating encephalomyelitis and porcine rotavirus were highly sensitive to interferon-beta, while swinepox, bovine herpesvirus type 1, porcine parvovirus, transmissible gastroenteritis and porcine enteroviruses were less sensitive than the above viruses to interferon-beta...

Detection of Anti-Hepatitis C Virus Effects of Interferon and Ribavirin by a Sensitive Replicon System

Kato, Takanobu; Date, Tomoko; Miyamoto, Michiko; Sugiyama, Masaya; Tanaka, Yasuhito; Orito, Etsuro; Ohno, Tomoyoshi; Sugihara, Kanji; Hasegawa, Izumi; Fujiwara, Kei; Ito, Kiyoaki; Ozasa, Atsushi; Mizokami, Masashi; Wakita, Takaji
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /11/2005 Português
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Although combination therapy with interferon and ribavirin has improved the treatment for chronic hepatitis C virus (HCV) infection, the detailed anti-HCV effect of ribavirin in clinical concentrations remains uncertain. To detect the anti-HCV effect of ribavirin in lower concentrations, a sensitive and accurate assay system was developed using the reporter replicon system with an HCV genotype 2a subgenomic replicon (clone JFH-1) that exhibits robust replication in various cell lines. This reporter replicon was generated by introducing the luciferase reporter gene (instead of the neomycin resistance gene) into the subgenomic JFH-1 replicon. To assess the replication of this reporter replicon, luciferase activity was measured serially up to day 3 after transient transfection of Huh7 cells. The luciferase activity increased exponentially over the time course of the experiment. After adjustment for transfection efficiency and transfected cell viability, the impacts of interferon and ribavirin were determined. The administration of interferon and ribavirin resulted in dose-dependent suppression of replicon RNA replications. The 50% inhibitory concentration of interferon and ribavirin was 1.80 IU/ml and 3.70 μg/ml, respectively. In clinical concentrations...

Effect of interferon on the induction of human monocyte secretion of interleukin-1 activity.

Newton, R C
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1985 Português
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This study investigates the effect of interferons on the induction of human monocyte secretion of interleukin-1 (IL-1) activity by lipopolysaccharides (LPS). Monocytes do not spontaneously produce IL-1 and the addition of interferons to the culture does not lead to detectable secretion. Addition of LPS alone induces the release of measurable amounts of IL-1 activity. The addition of low doses (1-10 units/ml) of alpha, beta, or gamma interferon to the LPS-stimulated cultures further increases this secretion by 50%. The addition of 1000 units/ml of alpha or beta interferon leads to inhibition of IL-1 release. By contrast, gamma interferon is a dose dependent enhancer of IL-1 release. The effect of gamma interferon is on the production of IL-1 and is not an enhancement of IL-1 activity in the biological assay. Results demonstrate that addition of gamma interferon to monocytes increases the rate of secretion of IL-1 by these cells. Gamma interferon also appears to abrogate the loss in the ability of monocytes to produce IL-1 activity after overnight culture. This last result parallels the maintainence of the expression of the HLA-DR surface marker on monocytes by gamma interferon. These results may help define a mechanism involving IL-1 generation which could have bearing on the in vivo pyrogenic effects of purified gamma interferon.

Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists▿

Kopecky-Bromberg, Sarah A.; Martínez-Sobrido, Luis; Frieman, Matthew; Baric, Ralph A.; Palese, Peter
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Português
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The severe acute respiratory syndrome coronavirus (SARS-CoV) is highly pathogenic in humans, with a death rate near 10%. This high pathogenicity suggests that SARS-CoV has developed mechanisms to overcome the host innate immune response. It has now been determined that SARS-CoV open reading frame (ORF) 3b, ORF 6, and N proteins antagonize interferon, a key component of the innate immune response. All three proteins inhibit the expression of beta interferon (IFN-β), and further examination revealed that these SARS-CoV proteins inhibit a key protein necessary for the expression of IFN-β, IRF-3. N protein dramatically inhibited expression from an NF-κB-responsive promoter. All three proteins were able to inhibit expression from an interferon-stimulated response element (ISRE) promoter after infection with Sendai virus, while only ORF 3b and ORF 6 proteins were able to inhibit expression from the ISRE promoter after treatment with interferon. This indicates that N protein inhibits only the synthesis of interferon, while ORF 3b and ORF 6 proteins inhibit both interferon synthesis and signaling. ORF 6 protein, but not ORF 3b or N protein, inhibited nuclear translocation but not phosphorylation of STAT1. Thus, it appears that these three interferon antagonists of SARS-CoV inhibit the interferon response by different mechanisms.

Interferon-γ Increases hPepT1-Mediated Uptake of Di-Tripeptides Including the Bacterial Tripeptide fMLP in Polarized Intestinal Epithelia

Buyse, Marion; Charrier, Laetitia; Sitaraman, Shanthi; Gewirtz, Andrew; Merlin, Didier
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /11/2003 Português
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Interferon-γ causes a global phenotypic switch in intestinal epithelial function, in which enterocytes become immune accessory cells. The phenotypic switch is characterized by a down-regulation of membrane transporters and up-regulation of immune accessory molecules in intestinal epithelial cells. However, the effect of interferon-γ on the intestinal epithelia di-tripeptide hPepT1 transporter has not been investigated. In this study we demonstrate that 1) interferon-γ increases di-tripeptide uptake in dose- and time-dependent manner in model intestinal epithelia (Caco-2 BBE cell monolayers), 2) the increase in di-tripeptides induced by interferon-γ is hPepT1 mediated, 3) interferon-γ does not affect the hPept1 expression at the mRNA and protein levels 4) interferon-γ increases the intracellular pH and consequently enhances the H+-electrochemical gradient across apical plasma membrane in model intestinal epithelia (Caco2-BBE monolayers). We suggest that interferon-γ could increase the hPepT1 mediated di-tripeptides uptake in inflamed epithelial cells. Under these conditions, interferon-γ will increase the intracellular amount of such diverse prokaryotic and eucaryotic small di-tripeptides in inflamed epithelial cells. The intracellular accumulation of such di-tripeptides may be important in enterocytes becoming immune accessory cells.

Interferon effects on microfilament organization cellular fibronectin distribution, and cell motility in human fibroblasts

Pfeffer, LM; Wang, E; Tamm, I
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/04/1980 Português
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We have shown previously (Pfeffer et al., 1979, Exp. Cell Res. 121:111-120) that treatment of human fibroblasts, planted at a density of 2x10(3) cells/cm(2), with purified human fibroblasts interferon (640 U/ml) for 3 d at 37 degrees C decreases the overall rate of cell proliferation to 35-40 percent of the control value. In the present experiments we have characterized the phenotype of interferon-inhibited fibroblasts. The mean volume of trypsinized, interferon-treated cells was increased 31 percent abover that of control cells. The interferon-treated population was much more heterogeneous than the control population with respect to volume, and there was a considerable overlap in the volume distributions of the two populations. The cell surface area was, on the average, increased 65 percent after interferon treatment. More than 80 percent of the treated cells had enlarged nuclei, many of which were lobed, and the fraction of binucleated cells was increased fivefold. After interferon treatment, over 40 percent of the cells showed large actin-containing fibers in the form of multiple parallel arrays. Fewer than 5 percent of the control cells contained such large actin fibers. The number of actin fibers of all sizes was tripled in the treated fibroblasts on a per cell basis and...

THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION : VI. INHIBITION BY HYDROCORTISONE OF INTERFERON SYNTHESIS IN THE CHICK EMBRYO

Smart, K. Marilyn; Kilbourne, Edwin D.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 31/01/1966 Português
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The initial observations that cortisone may act as an inhibitor of viral interference (11, 4) are now explicable as an inhibitory effect on interferon synthesis. The suggestion that the action of interferon is also inhibited by cortisone or its analogues (6) has not been confirmed in a plaque reduction type of interferon assay system in which autointerference by the challenge inoculum is a lesser problem. In this respect, the present results are in accord with those obtained by DeMaeyer and DeMaeyer (8) with hydrocortisone in a system in which a low multiplicity (0.1) Sindbis virus infection in monolayer culture was employed with cytopathic effect (CPE) as an end-point. It has been shown that hydrocortisone is restrictive to the synthesis of interferon induced by inoculation of either infective or inactivated virus into the chick embryo, and that this inhibitory effect is temporary. However, in another study in the chick embryo, three spaced injections of hydrocortisone (0.25 mg/dose) prevented the appearance of detectable interferon during the entire 64 hr observation period following inoculation of 103.3 EID50 of Lee virus (12). The importance of explicit definition of experimental conditions in assessing hormonal effects on infection is illustrated by the capacity of hydrocortisone either to inhibit or increase interferon synthesis in vitro...

Severity of lymphocytic choriomeningitis virus disease in different strains of suckling mice correlates with increasing amounts of endogenous interferon

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/09/1980 Português
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A marked difference was observed in the severity of disease in lymphocytic choriomeningitis (LCM) virus-infected suckling BALB/c, Swiss, and C3H mice. BALB/c mice had minimal liver lesions and none died, whereas C3H mice had extensive liver lesions and all mice died. An intermediate pattern was oberved for Swiss mice (36% mortality). Although there was no difference in the titers of LCM virus in the plasma or liver between these three strains of mice, there was a marked difference in the amount of interferon produced and the duration of interferonemia. C3H mice produced more interferon than Swiss mice which produced more interferon than BALB/c mice, indicating a direct correlation between the amount of interferon induced by LCM virus and the extent of disease. Inoculation of a potent anti-mouse interferon globulin markedly reduced the incidence of mortality in virus-infected C3H mice. BALB/c mice were as sensitive to the effects of interferon as C3H mice because daily administration of potent interferon preparations did induce disease in this strain. This ensemble of results supports our contention that endogenous interferon is in large part responsible for the manifestaions of acute LCM virus disease in suckling mice.

Injection of mice with antibody to interferon enhances the growth of transplantable murine tumors

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/12/1983 Português
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Injection of DBA/2, C57Bl/6, or BALB/c mice with antibody to mouse interferon alpha/beta enhanced the i.p. transplantability of six different murine tumors, as manifested by an increase in the percentage of tumor-bearing mice and a decrease in survival time. The effect was observed in mice injected with antibody to interferon raised in three sheep, a goat, and a rabbit, but not with sheep antibody to "impurities" present in the mouse interferon preparations or with normal sheep or goat globulins. The enhancement in transplantability was most marked when tumor cells had been previously passaged in vitro and were of low tumorigenicity. Analysis of some of the experimental conditions using interferon-sensitive and interferon-resistant lines of Friend erythroleukemia cells (FLC) showed that the enhancing effect was observed over a wide range of tumor cell inocula, was directly related to the amount of antibody to interferon injected and was most pronounced when antibody was administered at the time of tumor cell injection. Enhancement was also observed when FLC were injected subcutaneously (s.c.). Antibody did not act directly on the tumor cells in vitro. Although we were unable to demonstrate any biologically active interferon in mice before or after tumor cell inoculation...