Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “INTERFERON”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
PubMedDate not supplied

[The interferon reaction of the leukocytes and the natural killer activity in patients with acute viral hepatitis B undergoing interferon treatment].

The interferon response of leukocytes (IRL) alpha and gamma as well as the functional activity of natural killers (NK) were studied in patients with the verified diagnosis of acute viral hepatitis B (AVH-B) treated with leukinferon (a preparation of natural interferon-alpha and cytokines) and reaferon (recombinant alpha 2 interferon). The effect of therapy with LF and RF in patients with AVH-B manifested by an increase in the functional activity of NK up to complete normalization after termination of the course of therapy. In the group of patients treated with LF as a result of therapy IRL-alpha increased by the end of the treatment and in the convalescence period. The observed activation of NK and the IF-alpha system under the effect of IF preparations in patients with AVH-B correlated with enhanced elimination of HBsAg.

Acute Disease↗
PubMed1995

Expression of interferons-alpha and -beta, tumor necrosis factor-alpha and transcription factors, IRF-1 and IRF-2, in leukocytes induced during interferon production.

Analysis of gene expression in peripheral blood lymphocytes is of special interest because it could reflect physiological conditions. We have examined the expression and compared the relative amounts of specific mRNAs for interferons (IFN-alpha and IFN-beta), tumor necrosis factor-alpha (TNF-alpha) and interferon regulatory factors (IRF-1 and IRF-2) from interferon primed and Sendai virus induced peripheral blood leukocytes. Results obtained showed that IRF-1 was highly inducible by IFN treatment, IFN-alpha, TNF-alpha and IRF-2 were weakly induced by IFN treatment, and IFN-beta was not inducible by priming the cells with recombinant human IFN-alpha 2b. The IFN-alpha, IFN-beta, IRF-2 and TNF-alpha transcripts increased upon viral infection. The IRF-1 mRNA was rapidly induced by IFN treatment and decreased after Sendai virus infection. Our results show that, in peripheral blood lymphocytes, IFN-alpha and -beta genes have a different response to IFN induction, thus suggesting different regulatory mechanisms for IFN induction of type I IFN genes in peripheral blood lymphocytes.

DNA-Binding Proteins↗
PubMed2006

Potential for interferon beta-induced serum antibodies in multiple sclerosis to inhibit endogenous interferon-regulated chemokine/cytokine responses within the central nervous system.

BACKGROUND: A proportion of patients with multiple sclerosis (MS) receiving systemic interferon beta therapy will develop serum neutralizing antibodies (NAbs) that can reduce the activity of the drug. Interferon-beta (IFN-beta) is produced by glial cells within the central nervous system. Although systemic interferon beta does not access the central nervous system, titers of serum NAbs may be sufficient that some will access the central nervous system. OBJECTIVE: To address whether serum samples that contain high titers of NAbs could inhibit glial cell production of chemokines and cytokines that are regulated by endogenous IFN-beta. DESIGN: We used an in vitro assay involving toll-like receptor 3 ligand (polyinosinic-polycytidylic acid) signaling to assess the effect of serum samples containing high titers of NAbs (1800-20 000 U) on production of the chemokine CXCL10 and the cytokine interleukin 6 by human astrocytes. RESULTS: Serum samples positive for NAbs significantly inhibited polyinosinic-polycytidylic acid-induced CXCL10 and IL-6 production by astrocytes. CONCLUSION: High-titer NAbs to interferon beta may block endogenous IFN-beta function and alter the chemokine/cytokine microenvironment within the central nervous system, thereby modulating the profile and course of the local inflammatory response.

Adult↗
PubMed1978

Interferon and spontaneous cytotoxicity in man. I. Enhancement of the spontaneous cytotoxicity of peripheral lymphocytes by human leukocyte interferon.

A purified preparation of human leukocyte interferon used at this hospital in the treatment of malignant diseases was tested for its ability to modify the spontaneous cytotoxicity of peripheral lymphocytes from healthy donors. The inhibitory effect of allogeneic lymphocytes on the (3H)thymidine incorporation of a lymphoblastoid cell line, Raji, was augmented by the presence of interferon or by pretreatment of the lymphocytes with interferon. This form of pretreatment also increased lymphocytes' capacity for reducing the number of surface-adherent tumor cells in a microassay. Moreover, lymphocytes treated with interferon exhibited an enhanced cytotoxic capacity for target cells on incubation with such cells labelled with 51CR.

Cell Line↗
PubMed1979

Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. VI. Polyoma virus infection.

We have determined the effect of a single injection of potent sheep anti-mouse interferon globulin on polyoma-virus-induced early runting disease and tumor formation in Swiss mice. When newborn mice were injected with greater than or equal to 9 X 10(6) PFU of polyoma virus, 16% (7/44) of mice runted and died in contrast to 96% (45/47) of mice injected with virus and anti-interferon globulin. Likewise, a greater percentage of mice injected with lower doses of virus and anti-interferon globulin developed tumors than did control virus-injected mice. These results suggest that interferon is an important factor in determining the susceptibility of newborn mice to polyoma virus.

Animals↗
PubMed1982

Acquisition of tolerance to the antiproliferative activity of interferon by X-ray transformed C3H/10T1/2 cells under prolonged treatment with interferon.

X-ray-transformed C3H/10T1/2 cells serially passaged in the presence of highly purified mouse interferon appeared to acquire progressively a tolerance to the inhibitory effect of interferon on cell proliferation. In contrast, these cells did not appear to develop a tolerance to the antiviral activity of interferon. These results suggest the possibility that these two effects of interferon are mediated by different mechanisms.

Animals↗
PubMed1989

[Sensitivity of different cell lines to interferons: the relative antiviral activity as a function of the interferon subtype].

The phenomenon that rHuIFN-alpha1(D) displays an apparently higher antiviral activity when assayed on bovine cells as compared to human cell lines was applied to the elucidation of the nature of recombinant HuIFN prepared in our institute. These investigations were carried out by using a microtitre test, which defines biological activity as the IFN concentration leading to 50% inhibition of the cytopathic effect of vesicular stomatitis virus (VSV). In addition, the ability of IFN to diminish the reproduction of infectious viruses was monitored. The two methods yielded similar results. With bovine cells, antiviral activities of the same order of magnitude were observed, regardless of the interferon types applied, i.e. rHuIFN-alpha 1, rHuIFN-alpha 2 and human leukocyte interferon. On human fibroblasts, however, rHuIFN-alpha 1 had an apparently 45 to 165 times lower activity than the other two interferons. On human WISH cells, the differences in apparent activity between the respective IFNs were even greater, with factors of up to 212 fold being observed. Still more distinctive were the effects on murine L 929 cells where an antiviral effect could be confirmed only for rHuIFN-alpha 1 whereas the other two interferons proved completely inactive.

Animals↗
PubMed1985

Treatment of plasma cell neoplasm with recombinant leukocyte A interferon and human lymphoblastoid interferon.

Thirty cases of plasma cell neoplasms (24 multiple myeloma, one plasma cell leukemia, and three primary macroglobulinemia) were treated with two kinds of highly purified alpha-interferons, recombinant human leukocyte interferon (rIFN-alpha A) (16 cases) and human lymphoblastoid interferon (HLBI) (14 cases). Partial remission (PR) was obtained in two of 16 evaluable cases treated with rIFN-alpha A and in two of 12 evaluable cases treated with HLBI. If minor response (MR) was included, responses were observed in seven (31.3%) and six (50%), respectively. Response (PR + MR) was noted in 38% of 21 previously treated patients and 71% of seven previously untreated patients. Side-effects were noted in more than two-thirds of the patients. They included fever, malaise, nausea/anorexia and myelosuppression. Thus, these two kinds of highly purified alpha-interferon were effective in plasma cell neoplasm, producing unequivocal response in 14.3% of the cases without unacceptable side-effects.

Aged↗
PubMed1999

[Interferon-alpha-associated polyarthritis. Possible induction of seropositive rheumatoid arthritis by interferon-alpha: two case reports and review of the literature].

We describe a patient with chronic myelogenous leukemia (CML) and a patient with hairy cell leukemia being effectively treated with alpha-interferon who developed a seropositive chronic polyarthritis formally fulfilling the ACR criteria for rheumatoid arthritis. Because of its efficacy, interferon was not discontinued, and the arthritis treated with low-dose prednisolone or NSAIDS. These are the 19th and 20th case of symmetrical polyarthritis during alpha-interferon therapy fulfilling the criteria for RA. The possible mechanisms of the relatively frequent appearance of autoimmune diseases during interferon therapy are discussed.

Anti-Inflammatory Agents↗
PubMed1989

Effective method for obtaining long nucleotide chains on partially complementary templates. Processed bovine gamma-interferon gene obtained from human gamma-interferon gene.

The method of obtaining the bovine gamma-interferon gene by means of simultaneous multidirected mutagenesis of the human gamma-interferon gene is presented. The first strand of the bovine gamma-interferon gene was obtained by ligation of synthetic oligonucleotides, using the cDNA of human gamma-interferon, cloned in the single-stranded phage M13mp19 as a template. The second strand was synthesized using a large fragment of E. coli DNA-polymerase I. The double-stranded gene was then treated by restriction nucleases and cloned in a pUC-18 derived vector. The primary structure was confirmed by sequencing.

Animals↗
PubMed1986

Friend murine leukemia virus and spleen focus-forming virus expression in highly malignant interferon-sensitive and interferon-resistant Friend leukemia cells.

Analysis of expression of the Friend murine leukemia virus (F-MuLV) and of the spleen focus forming virus (SFFV) has been undertaken in highly malignant interferon (IFN)-sensitive (745) and IFN-resistant (3Cl-8) Friend leukemia cells (FLC), serially passaged intraperitoneally in DBA/2 mice. In vivo passaged 745 cells, as well as the clones derived thereof, did not release Friend virus (FV). Western blot analysis of the plasma membrane fractions of the virus nonproducer 745 cells revealed the lack of gp69/70 glycoprotein expression. At least 10 intraperitoneal passages of virus producer in vitro passaged of virus producer in vitro passaged 745 cells were necessary to obtain the selection of the virus nonproducer phenotype. In contrast in vivo passaged 3Cl-8 cells continued to produce FV even after 100 in vivo passages and expressed gp69/70 antigens to a similar extent as the original in vitro passaged FLC. The expression of F-MuLV and SFFV RNAs in virus producer and virus nonproducer FLC clones has been investigated by means of Northern blot technique using probes specific for either F-MuLV or SFFV. No F-MuLV specific RNA sequences were detected in virus nonproducer 745 clones. SFFV specific RNA transcripts and gp52/55 glycoprotein production could be revealed in all the FLC tested. Southern blot analysis showed the presence of F-MuLV specific sequences in the cellular DNA of virus nonproducer 745 clones. As both in vivo passaged F-MuLV producer 3Cl-8 and F-MuLV nonproducer 745 cells were equally barely immunogenic and highly malignant when injected into syngeneic DBA/2 mice, these results indicate that F-MuLV expression does not result per se in a high immunogenic potential of tumor cells. For the time being, as a specific property of 3Cl-8 versus 745 cells is the interferon-resistant phenotype, it is tempting to speculate that the selection of virus nonproducer cell variants after in vivo passages of interferon-sensitive 745 cells could depend on the presence of low levels of endogenous interferon in normal young mice.

Animals↗
PubMed1988

Interferons as gene activators: close linkage of two interferon-activatable murine genes.

Previously we have identified a mouse genomic clone (clone 5) which specifies the 5' flanking region and the 5' terminal exon of an interferon-activatable gene (202 gene). Here, we show that about 5 kb upstream from this flanking region in clone 5 there occurs a 3' terminal region of a second interferon-activatable gene (203 gene). The two genes are transcribed in the same direction. Segments from the 203 gene can be hybridized to a set of five interferon-inducible RNAs. The 203 mRNAs are induced about 15-fold in interferon-treated Ehrlich ascites tumor cells.

Animals↗
PubMed1978

Interferon-associated, dsRNA-dependent enzyme activities in a mutant 3T6 cell engaged in the semiconstitutive synthesis of interferon.

Cytoplasmic extracts of untreated cultures of a virus-resistant mutant of mouse 3T6 cells, designated 3T6-VrB2, contain two double-stranded, RNA-activated enzyme activities associated with interferon action. These are the synthesis of a low molecular weight oligonucleotide inhibitor of cell-free protein synthesis from ATP, and the phosphorylation of a 67,000 dalton polypeptide by transfer of the gamma phosphate of ATP. Basal levels of both enzyme activities are detectable in extracts of untreated parental 3T6 cells, and are greatly enhanced upon interferon pretreatment. A procedure was developed, using a nonionic detergent to effect cell lysis, which allowed the analysis of the protein kinase activity from as few as 2 x 10(7) cells. Using this procedure, direct proportionalities were demonstrated between the concentration of interferon to which 3T6 cells were exposed, and both the level of protein kinase activity and the magnitude of the antiviral state were established in these cells. Furthermore, untreated cultures of 3T6-VrB2 exhibited both an antiviral state and an intracellular protein kinase activity equal to that of cultures of the parental 3T6 cells pretreated with a single concentration of mouse interferon.

Cell Line↗
PubMed1983

Interferon action: two (2'-5')(A)n synthetases specified by distinct mRNAs in Ehrlich ascites tumor cells treated with interferon.

(2'-5')(A)n synthetase and RNAase L (a latent endoribonuclease) are among the mediators of interferon action. The product of (2'-5')(A)n synthetase (i.e., (2'-5')(A)n) binds, and thereby activates RNAase L. Interferons induce in Ehrlich ascites tumor (EAT) cells two mRNAs (sizes 1.5 kb and 3.8 kb), which can be translated in Xenopus oocytes into (2'-5')(A)n synthetases of 20,000 to 30,000 daltons and 85,000 to 100,000 daltons, respectively. (2'-5')(A)n synthetases of corresponding sizes are induced by interferons in EAT cells. In the cell extract the bulk of the larger enzyme is in the cytoplasmic fraction, and the bulk of the smaller one in the nuclear fraction. The only known function of (2'-5')(A)n is the activation of RNAase L, and RNAase L can be selectively crosslinked to a (2'-5')(A)n derivative in a cytoplasmic extract from EAT cells. The same (2'-5')(A)n derivative can be crosslinked to several proteins in the nuclear extract of EAT cells, and some of these proteins are induced by interferon.

2',5'-Oligoadenylate Synthetase↗
PubMed1996

Interferon activity of mitogen-induced chicken splenic lymphocytes which do not express interferon mRNA.

Interferon activity was measured in media from virally infected chicken embryo fibroblasts and Concanavalin A-stimulated splenic lymphocytes using a viral inhibition assay. Both cell types produce interferon activity. A cDNA probe corresponding to a chicken interferon mRNA was used to probe Northern blots of RNA prepared from both cells. A single hybridizing species of 900 bases was detected in virally infected fibroblast RNA, but no hybridizing species was detected in the splenic lymphocytes. These results suggest that the interferon activity produced by lymphocytes is of different molecular origin than the corresponding activity produced by virally infected fibroblasts.

Animals↗
PubMed2005

Pharmacogenomics of responsiveness to interferon IFN-beta treatment in multiple sclerosis: a genetic screen of 100 type I interferon-inducible genes.

OBJECTIVES: Interferon IFN-beta is indicated for the treatment of multiple sclerosis. A significant proportion of patients show a poor clinical response to therapy. Type I interferon exerts its effect at least partially through interaction of specific transcription factors with interferon-stimulated response elements (ISREs), mostly located in promoter regions of its target genes. We hypothesized that polymorphisms may occur within or close to ISRE elements, altering type I interferon inducibility and ultimately leading to a modified clinical response in carriers. METHODS: We selected 100 ISRE-containing genes and sequenced their promoter regions in small genomic deoxyribonucleic acid pools of responding and nonresponding patients, as well as healthy control subjects. A selection of polymorphisms discovered by this approach was scrutinized subsequently in a collection of individual deoxyribonucleic acid samples. RESULTS: We identified 4 genes containing polymorphisms associated with response to recombinant IFN-beta: IFNAR1 (P = .036), LMP7 (P = .002; odds ratio [OR], 6.37 [95% confidence interval (CI), 1.84-24.1]), CTSS (P = .02; OR, 0.38 [95% CI, 0.18-0.84]), and MxA (P = .015; OR, 3.37 [95% CI, 1.11-11.4]). Logistic regression analysis with treatment outcome used as the dependent variable and genotype as the independent variable revealed 2 genes, LMP7 (OR, 0.55 [95% CI, 0.34-0.89]) and MxA (OR, 0.41 [95% CI, 0.19-0.88]), that were independently associated with treatment response. CONCLUSIONS: Our work confirms and extends previous indications for a polygenic mechanism involved in bringing about responsiveness to recombinant IFN-beta. The identification of 2 genes active in the antigen processing and presentation cascade; that is, LMP7, coding for the proteasome subunit beta, and CTSS, coding for cathepsin S; as potential response modifiers may identify this pathway as being of particular relevance to phenotypic expression of response heterogeneity.

Chromosome Mapping↗
PubMed1997

Quasispecies nature of hepatitis C virus and response to alpha interferon: significance as a predictor of direct response to interferon.

BACKGROUND/AIMS: We evaluated the significance of the quasispecies nature of HCV as a predictor of the response to alpha interferon therapy in patients with chronic hepatitis C. METHODS: Natural alpha interferon was administered in 62 patients for 24 weeks (daily for 2 weeks, then three times weekly for 22 weeks) and factors were analyzed that could affect the response. HCV subtype, HCV RNA concentrations and the number of HCV quasispecies were evaluated before treatment. HCV RNA concentrations were measured by branched DNA probe assay. The number of HCV quasispecies was measured by fluorescence single-strand conformation polymorphism analysis. RESULTS: The HCV RNA concentration (p < 0.0001), HCV subtype (p = 0.0076), and the number of HCV quasispecies (p = 0.0024) were significantly associated with a complete response. Multivariate analyses showed that the number of HCV quasispecies was an independent predictor of the disappearance of HCV RNA during the administration of alpha interferon, but did not predict a relapse after its completion. Pretreatment concentration of HCV RNA was the only factor that was related to a long-term disappearance of HCV RNA. CONCLUSIONS: The number of HCV quasispecies was significantly related to the response to alpha interferon early in its administration. The pretreatment concentration of HCV RNA was mainly related to a relapse following completion of treatment.

Adult↗
PubMed1999

Long-term efficacy of treatment of chronic hepatitis C with alpha interferon or alpha interferon and ribavirin.

The major objective of treatment of chronic hepatitis C virus (HCV) infection is to prevent progression to cirrhosis, and thereby prevent complications of end-stage liver disease. The established treatment of chronic HCV is with alpha interferon. Recent results with ribavirin and alpha interferon together suggest that combination antiviral therapy will become the benchmark treatment. For both naive and relapsed patients, however, it has become important to assess the long-term outcome of treatment, in order to gauge whether treatment has indeed modified the natural history of chronic hepatitis C virus infection. It seems likely that most sustained responders (85-90%) treated with combination ribavirin and alpha interferon will continue to have a long-term biochemical and virological response, as has been demonstrated with alpha interferon alone, but further long-term follow-up of patients treated with combination therapy is required.

Antiviral Agents↗