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At least 1,009 records · Page 56Linked to original sources
PubMed2003

Leucocyte interferon-alpha for patients with chronic hepatitis C intolerant to other alpha-interferons.

BACKGROUND: Alpha-interferon (alpha-IFN) is the treatment of choice for chronic hepatitis C but most patients experience adverse effects which sometimes lead to the suspension of therapy. Recently, higher doses of alpha-IFN or prolonged therapy have increased the number of cases of intolerance. STUDY DESIGN: In this open study we evaluated the efficacy and safety of leucocyte interferon-alpha (IFNalpha) [6MU three times a week] in 43 patients with chronic hepatitis C who had been intolerant to previous treatment courses with recombinant or lymphoblastoid IFNalpha. All patients were treated for 6 months and followed-up for an additional 6 months.End of treatment responders were patients in whom hepatitis C virus (HCV)-RNA had been eradicated from the blood by the end of treatment, sustained responders were those patients who maintained negative HCV-RNA at the end of follow-up, and the remaining patients were considered non-responders. Adverse effects were monitored by interviews, laboratory and clinical examinations. RESULTS: Five patients (11.6%) discontinued the treatment, four due to the reappearance of previous adverse effects, and one due to an ex novo adverse effect. In six patients the dose had to be halved. At the end of treatment 11 patients (25.6%) had negative serum HCV-RNA. After discontinuation of therapy, disease flared in four patients, thus seven patients were sustained responders. CONCLUSIONS: This study shows that leucocyte IFNalpha at a dose of 6MU three times a week is well tolerated in patients previously intolerant to recombinant or lymphoblastoid IFNalpha, allowing a high percentage of them to complete a course of treatment in terms of duration and dose.

Antiviral Agents↗
PubMed2006

Induction therapy with twice-daily interferon-beta does not improve the therapeutic efficacy of consensus interferon monotherapy for chronic hepatitis C.

We examined therapeutic superiority of induction therapy with twice-daily IFN-beta (3X2=6 million units/day) onto 6-months consensus interferon monotherapy for chronic hepatitis C. Patients were randomly assigned to monotherapy without (group I, n=16) and with induction therapy (group II, n=12). The mean age of group II was older than that of group I, and other baseline condition was not statistically significant. Sustained virological response (SVR) rates of group I and II were 81.3% (13/16) and 58.3% (7/12), respectively (p=0.365). SVR rates in patients with genotype 1b were 66.7% (4/6) and 0% (0/2, because of drop-out), and those with high viral load were 70% (7/10) and 75% (6/8) in group I and II, respectively (p=1.000). Drop-out rates during therapy were 6.3% (1/16) and 33.3% (4/12) in group I and II, respectively (p=0.176). Age less than 50 years was the only independent factor that was shown by multivariate logistic model analysis to be associated with a sustained virological response. Although randomization failed to produce and equal age distribution in the two groups in this study, our results suggest that induction therapy with twice-daily IFN-beta has no beneficial effect on the efficacy of monotherapy with consensus interferon, probably because of the higher drop-out rates and incidence of adverse reactions with induction therapy.

Female↗
PubMed1984

Synergism of antiviral activity in cell cultures treated with low concentrations of interferon and interferon-treated lymphocytes.

Human T cells treated with low levels of interferon (IFN) (1-10 units/ml), and washed to remove the IFN, transferred the same level of antiviral activity to recipient WISH cells as an equivalent IFN treatment alone could induce in WISH cells. Further, when T cells pretreated with IFN (1-10 units/ml) were cocultivated with WISH cells in the presence of IFN (1-10 units/ml), a 2.5- to 5-fold greater level of protection developed than could be expected from the additive effect of each. Antibody to leukocyte, fibroblast, or immune IFN blocked the antiviral effect of the respective IFN types but had no effect on the transfer of antiviral activity initiated by leukocyte, fibroblast, or immune IFN. Also, treatment of T cells with actinomycin D blocked the transfer of antiviral activity of IFN-treated T cells. Taken together, the data suggest that the increased antiviral activity is not merely an additive effect of the IFN, but represents a synergistic amplification of protection most likely due to the combination of the separate effects of IFN and IFN-induced transfer. Such interactions would be expected to play a major role in early protection against virus infections in vivo when low levels of interferon are present and lymphocytes are migrating into the area.

Amnion↗
PubMed2001

[Autologous transplantation of peripheral hematopoietic cells and subsequent maintenance therapy with interferon alpha or interferon alpha and dexamethasone in patients with multiple myeloma--results from the 4W randomized clinical trial of the Czech Myeloma Group].

In the clinical 4W study patients with newly diagnosed multiple myeloma are included where the state of the disease calls for treatment, while high dose chemotherapy is not contraindicated. Treatment according to protocol 4W comprises induction chemotherapy VAD, mobilization of haematopoietic cells (cyclophosphamide 5 g/m2). This is followed by autologous transplantation (as a conditioning regime melfalan 200 mg/m2 is administered). The patients are randomized into two groups, the first one is given interferon alpha as maintenance treatment, in the second group alternates cyclically interferon alpha and dexamethasone treatment. So far between 1996 and Aug. 31 2000 in the 4W clinical study 167 patients were included. 113 patients after transplantation were evaluated incl. 13 (12%) who achieved complete remission of the disease (absence of paraprotein, negative immunofixation), 63 patients (56%) with remission of the disease (decline of paraprotein, by more than 75%). Another 24 patients (21%) achieved partial remission (decline of paraprotein by more than 50% but less than 75%). The peritransplantation mortality is 2.67%. So far there is no significant difference between the two groups on maintenance treatment as regards the mean period before a relapse of the disease (p = 0.567). The median of the mean survival was not reached so far. The authors describe the results of the internal analysis of data incl. statistical processing.

Adolescent↗
PubMed2002

[ROC curve analysis of factors predictive of response to treatment with interferon plus ribavirin in patients with chronic hepatitis C relapse after previous interferon treatment].

This study aimed to identify the factors predictive of response before the initiation of treatment and throughout the treatment period in patients with chronic hepatitis C relapse after treatment with interferon-a who were retreated with a standard regimen of interferon-a plus ribavirine and followed up for 40 months. Forty-four patients (40 with genotype 1, four without genotype 1) were included in the study. Four patients (genotype 1) were excluded because of adverse effects. The rate of maintained response was 55% (50% genotype 1, 100% non-genotype 1). The stage of histological damage (>2), glutamic-pyruvic transaminase (GPT) concentration (< or = 26 UI/l) and the association between the GPT concentration and the detection of the RNA-HCV in the first and third treatment months were the variables with an area under the ROC curve and a confidence interval >0.5. The probability of predicting a maintained response (negative predictive value) if the stage of histological lesion was <2 was 62.9%, while the positive predictive value was 100%. During the treatment, the disappearance of the RNA-HCV together with GPT values < or =26 in the first treatment month were the best predictive values. In this case, the negative predictive value was 78.3% and the positive predictive value was 76.5% (OR: 11.7, 2.6-52.2). Furthermore, the GPT value with the best predictive value (<26 UI/l) was a more effective predictor of the response to treatment than the normal value of the GPT. Finally, the GPT values >26 UI/l and the detection of RNA/HCV in the first or third treatment month were certain predictors of the absence of response but with low sensitivity (10-12%). It was concluded that is possible to predict the response to the combined treatment with an acceptable level of confidence, although not unequivocally. Ninety percent of the patients would be candidates for maintaining treatment for at least 6-12 months, while approximately 10% could undergo early interruption of treatment due to the absence of response.

Adult↗
PubMed1992

Mechanism of interferon action. cDNA structure and regulation of a novel splice-site variant of the catalytic subunit of human protein kinase A from interferon-treated human cells.

A molecular cDNA clone (KIN27) was isolated that encodes a novel variant of the catalytic subunit C alpha of the human cyclic AMP-dependent protein kinase (PKA). Analysis of PKA genomic sequence data revealed that the KIN27 variant transcripts likely result from alternative splice-site selection of the C alpha gene transcripts. The KIN27 cDNA has therefore been designated C alpha 2. RNA amplification by polymerase chain reaction revealed that KIN27 C alpha 2 splice-site variant RNA and PKA C alpha RNA were both expressed in the amnion U and HeLa human cell lines. C alpha RNA was about 3- to 5-fold more abundant than C alpha 2 RNA. Interferon treatment decreased the steady-state amount of the C alpha 2 RNA relative to C alpha RNA. These results suggest that alternative splicing may contribute to the structural heterogeneity of C subunits expressed in human cells and that interferon may affect this process.

Amino Acid Sequence↗
PubMed1992

[Effect of interferon and interferon combined with 3-methylcholanthrene on the mixed function oxidase system in the liver of mice].

The authors have studied the effect of human interferon alpha alone, as well as its effect when co-administered with 3-methylcholanthrene, on the mixed function oxidase system (MFO) of mouse liver. The single interferon alpha treatment did not influence the activities of MFO. However it decreased significantly the enzyme-inducing effect of 3-methylcholanthrene during combined treatment.

Animals↗
PubMed1991

Induced factor binding to the interferon-stimulated response element. Interferon-alpha and platelet-derived growth factor utilize distinct signaling pathways.

Interferon-alpha (IFN alpha) and platelet-derived growth factor (PDGF) each rapidly stimulate binding of nuclear factors from Balb/c 3T3 fibroblasts, to a 29-base pair regulatory sequence derived from the 5' upstream region of the murine 2-5A synthetase gene. This regulatory sequence contains a functional interferon-stimulated response element (ISRE) and also functions as a PDGF-responsive sequence. We show that IFN alpha induces binding of a protein of molecular mass 65 kDa to the ISRE. Constitutively expressed ISRE-binding proteins of 98 and 150 kDa are also demonstrated. Binding of inducible factors to the ISRE increases significantly within 15 min of IFN alpha or PDGF treatment. PDGF-induced binding is not mediated by IFN beta. The protein kinase inhibitors, staurosporine and K252a, block PDGF-induced ISRE binding and 2-5A synthetase gene expression. IFN alpha-induced ISRE binding and gene activation are not blocked by these inhibitors. Treatment of cells with 12-O-tetradecanoyl-13-acetate or dibutyryl cyclic AMP does not activate ISRE binding factors or 2-5A synthetase gene expression. PDGF responsiveness of the ISRE in vivo is also sensitive to staurosporine, indicating that inhibition of a protein kinase activity blocks the PDGF-specific transcriptional signal. Our data indicate the signal transduction pathway for IFN alpha-induced, ISRE-dependent transcription is distinct from the PDGF-induced ISRE response and is likely independent of cyclic AMP-dependent protein kinase and protein kinase C activities.

2',5'-Oligoadenylate Synthetase↗
PubMed1990

[The immunomodulating action of interferon preparations. The effect of medicinal alpha-interferon preparations on the rosette-forming activity of human blood lymphocytes].

Effects of alpha-interferon (alpha-IF) medical preparations on human blood lymphocyte rosette-forming activity was under study. Blood samples from 40 donors and 81 patients with chronic pyoderma, lupus erythematosus, and pemphigus were examined. Interferon preparations alpha-IF for nasal administration and IN-1 and IN-2 (or leukinterferon) for injections were used. The results evidence that IF preparations activities depend on the methods of the preparation synthesis and purification. alpha-IF and leukinterferon most effectively enhanced the lymphocyte ability to spontaneous, early, and active rosette formation. IN-1 was found less active and enhanced only the ability to spontaneous E-rosette formation, but had no effect on early active E-RFC subpopulations. IF preparations elevated the counts of E-RFC anf active RFC only if these levels were lowered; if these values were normal the agents had no effect.

Adjuvants, Immunologic↗
PubMed1987

Mid-term observations on the efficacy of alpha-interferon in hairy cell leukemia and status of the interferon system of patients in remission.

We summarize our experience using alpha-interferon (IFN-alpha) in the treatment of 93 patients with hairy cell leukemia. Both partially purified interferon and recombinant IFN-alpha produced over 85% response rate. Equal efficacy at 12 months of treatment was found for both types of IFN-alpha. However, continuation of treatment up to 24 months with partially purified IFN-alpha resulted in an increased number of complete remissions. An increase in the number of bone marrow's hairy cells occurred in 70-80% of the patients in whom a treatment was discontinued. Only 20% of the patients required reinitiation of treatment, and in all, reinduction of remission was readily obtained. Toxicity to IFN-alpha in patients with hairy cell leukemia was minimal. IFN-alpha production by patients in remission was studied. Only those patients in complete remission showed adequate IFN-alpha production. The role of endogenous IFN-alpha in the induction and sustenance of remission in hairy cell leukemia is discussed.

Humans↗
PubMed1986

A sensitive radioimmunoassay for alpha-interferon: circulating alpha-interferon-like substance in the plasma of healthy individuals and rheumatoid arthritis patients.

A radioimmunoassay for circulating alpha-interferon (IFN alpha) has been developed using lymphoblastoid IFN alpha. The assay was specific for IFN alpha, and did not cross-react with IFN beta, IFN gamma, or ACTH, while it was specifically inhibited by recombinant IFN alpha. The radioimmunoassay (y) correlated linearly with the virus inhibition assay (x), with a regression line of y on x of y = 0.659x + 245 (u) (P less than 0.01). alpha-Interferon-like substance (IFN alpha-LS) was extracted and concentrated from plasma either by silicic acid or by antibody immunoadsorption. Serial dilutions of plasma and extracted samples of plasma showed dilution curves identical to those of standard IFN alpha, suggesting the presence of endogenous IFN alpha in human plasma. The circulating IFN alpha-LS of healthy individuals aged 20 to 45 was 0.207 +/- 0.055 ng/ml in males (n = 48) and 0.172 +/- 0.076 ng/ml in females (n = 34). Gel filtration studies on a Sephadex G-75 column suggested that circulating IFN alpha-LS exists in a fragmented form, inactive in virus inhibition assays, in the plasma of healthy individuals. The finding may help explain why biological IFN alpha is often undetectable in the plasma of healthy donors, yet is detectable by radioimmunoassay. Circulating IFN alpha-LS in the plasma of healthy individuals declined gradually with age. IFN alpha-LS was significantly decreased in the plasma of rheumatoid arthritis patients, when compared with the value found in the age and sex-matched healthy controls and in osteoarthritis patients (P less than 0.0001). The decrease was related neither to treatment nor to disease activity. IFN alpha-LS was, however, not decreased in the plasma of vasculitis patients. Decreased IFN alpha-LS in rheumatoid arthritis may be important from pathogenetic and therapeutic standpoints.

Adult↗
PubMed1985

Cloning of a bovine interferon-alpha gene subfamily and comparisons between genetically engineered and leukocyte bovine interferons.

Bovine peripheral leukocytes were virally induced for interferon production, and an acid stable, SDS stable, antiviral activity was detected in the preparation. This bovine interferon (BoIFN) was tested for its ability to induce an antiviral state in various mammalian cells and was found to be specific to cells from bovine origin. The BoIFN cross reacts with antibodies against human IFN-alpha but these antibodies do not neutralize the bovine IFN activity. Leukocyte BoIFN exhibits polymorphism upon Affi-Gel Blue chromatography and SDS-PAGE (16k and 24K). The virally induced leukocytes produce a 13S mRNA which upon translation in oocytes yields an active IFN molecule. Bovine genomic library was constructed and screened for BoIFN-alpha sequences, using human IFN-alpha probes. From the clones isolated, five were found to represent distinct genes. Sequence analysis indicate that these genes are closely related (94% homology). One of these genes was expressed in E. coli under the control of trp promoter operator. The physicochemical and biological properties of the bacterial BoIFN-alpha product resemble those of a subpopulation of natural BoIFN.

Animals↗
PubMed1985

The physiological interferon response. V. Antiviral activity present in rat lymph is neutralized by anti-mouse interferon-gamma antibodies.

By neutralization tests using anti-rat and mouse interferon (IFN) antibodies, we tested whether the antiviral activity present in abdominal lymph but absent in plasma of healthy rats, could be ascribed to IFN. Antimouse IFN-gamma antibodies neutralized the inhibitor completely while anti-rat IFN-alpha/beta antibodies did not. We conclude that rat lymph contains traces of IFN-gamma and that the antiviral activity is not due to low-density lipoproteins, immunoglobulins, or to cell-produced viral inhibitors. This finding extends previous observations on rabbit lymph and further supports the existence of a physiological low-level interferon response.

Animals↗
PubMedDate not supplied

Treatment of lymphoid neoplasias with interferon. I. Human fibroblastic beta-interferon in malignant gammapathies. Phase II trial.

18 patients with malignant gammapathies (16 with myeloma and 2 with Waldenström's disease) were treated with human fibroblastic Interferon (beta IF). This was administered i.v. 6 X 10(6) units weekly (7 patients) or 3 X 10(6) units twice weekly (11 patients). during at least 3 months if tolerated. Treatment was discontinued because of side effects in three patients. Reduction of the M component, by at least 25% from the initial value, was obtained in 3 patients. In one case the disappearance of a urinary Bence Jones protein was observed. In 4 cases, there was a significant reduction of bone marrow infiltration by plasma cells. In 5 cases, major alleviation or disappearance of bone pain was observed. Duration of treatment seemed to be an important factor for activity. Immune monitoring with currently available tests, mainly natural cytoxicity, yielded no correlation with therapeutic effect in these patients. This preliminary study demonstrates the effect of fibroblastic Interferon in myeloma. However, further studies are necessary to determine the population of patients most likely to benefit from treatment, the best modalities, possible special indications, dose schedules and duration of treatment. As it is not myelosuppressive it could be indicated in the frequent situation of advanced myeloma with bone marrow failure, contra-indicating combination chemotherapy.

Aged↗
PubMed1982

[Treatment of leukemias and lymphomas with interferons: I. Trial of myeloma therapy with human beta-interferon].

Eighteen patients with malignant gammapathies (16 with myeloma and 2 with Waldenström's disease) for a short time because in a phase II-I trial were treated with human (IF beta) given i. v. 6 X 10(6) units weekly (7 patients) or 3 X 10(6) units twice weekly (11 patients) during at least 3 months if tolerated. Treatment was discontinued because of side-effects in three patients. Reduction of the M component of at least 25% from the initial value was obtained in 3 patients. In one case, was also observed in disappearance of the urinary Bence-Jones protein, in 4 cases a significant reduction of bone marrow infiltration by plasma cells and, in 5 cases, major alleviation or disappearance of bone pain. Length of treatment seems an important factor for activity. Immune monitoring with currently available tests, mainly NK cell activity, yielded no correlation with therapeutic effect in these patients. This very preliminary study demonstrates the effect of fibroblastic interferon in myeloma, but further studies are mandatory to determine the population of patients likely to benefit from treatment, the best modalities, possible special indication, dose schedule and duration of treatment. Interferon, however, already appears in this population of patients as giving results similar to those of single agent chemotherapy. As it is not myelosuppressive, it could be indicated in that frequent situation of advanced myeloma with bone marrow failure contra-indicating combination chemotherapy.

Clinical Trials as Topic↗
PubMed1983

Modulation of 5-fluorouracil-induced toxicity in mice with interferon or with the interferon inducer, polyinosinic-polycytidylic acid.

Partially purified preparations of mouse interferon, administered during the 2-day period following the administration of a toxic dose of 5-fluorouracil (FUra), yielded significant protection from mortality in BALB/c X DBA/2 F1 mice. Protection against FUra-induced toxicity was also observed when the interferon inducer polyinosinic-polycytidylic acid (poly I X poly C) was administered with FUra. The temporal relationship between the administration of poly I X poly C and FUra was found to be a critical determinant of the intensity of toxic manifestations. In relation to FUra alone, poly I X poly C could enhance (when administered 48 hr before FUra), diminish (when administered together with FUra), or not affect (when administered 48 hr after FUra) the degree of resultant toxicity. Cytofluorometric analysis of the DNA content of bone marrow cells indicated a transient period (about 42 hr) of inhibition of cell cycling following the administration of poly I X poly C, followed by reentry into cycle (between 42 and 66 hr) and a return to normal cycle phase distribution by 90 hr. This disturbance of the kinetic pattern of cell cycling in bone marrow would explain the administration time-dependent variability of the effect of poly I X poly C on FUra toxicity, since FUra is known to be a cell cycle-specific cytotoxic drug. Potential practical application of this observation to the clinical use of FUra in cancer therapy is discussed.

Animals↗
PubMed1983

[Review of the recent advances on interferon and interferon therapy].

Interferon is a glycoprotein that has antiviral activity. Recently, important advances have been obtained about it's purification, pharmacological effects and side effects and spectrum. It's clinical applications have increased in the treatment the viral and tumoral diseases. It is been reported that the good results have been obtained in the treatment of varicella zoster and other herpetic viruses, cytomegalovirus Epstein-Barr virus, hepatitis B virus infections and in the viral infection of the respiratory tracts. In this article, the recently advances about interferon and it's use in the treatment of viral infections have been reviewed.

Chickenpox↗