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Results for “Interferon-beta”

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At least 127 records · Page 7Linked to original sources
PubMed1992

Modulation of leukemic cell sensitivity to lymphokine-activated killer cytolysis: role of intercellular adhesion molecule-1.

The role of CD11/CD18 leukocyte adhesion molecules and their ligands in mediating non-major histocompatibility complex (MHC) restricted lymphocyte cytotoxicity is controversial. In order to examine the role of target cell intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of lymphocyte function-associated antigen (LFA-1) (CD11a/CD18), we exposed the human leukemia cell line, HL-60, to a variety of agents implicated in modulating ICAM-1 expression and/or sensitivity to lymphocyte cytolysis. Exposure of HL-60 cells to retinoic acid (RA), interferon (IFN)-alpha, IFN-beta, and IFN-gamma induced protection from lymphokine-activated killer (LAK) cytolysis. Only RA and IFN-gamma induced ICAM-1 expression. Tumor necrosis factor and vitamin D3, which also induced ICAM-1 expression, increased HL-60 sensitivity to LAK lysis. Granulocyte-macrophage colony-stimulating factor also increased sensitivity to LAK lysis; ICAM-1 was not induced. The state of cellular differentiation and expression of class I and II MHC antigens also did not correlate with sensitivity to LAK cytolysis. Exposure of untreated HL-60 cells and HL-60 cells expressing ICAM-1 to monoclonal antibody (mAb) versus ICAM-1 did not modulate LAK sensitivity. Exposure of LAK cells to mAb versus LFA-1 partially inhibited cytolysis; mAb versus CD18 inhibited cytolysis more completely. HL-60 cells were resistant to natural killer lysis; exposure to the various experimental agents did not alter sensitivity. We conclude that leukemic cell sensitivity to LAK cytolysis can be modulated by a variety of agents. Although our results suggest a role for leukocyte CD11/CD18 adhesion molecules in LAK cytolysis, the poor correlation between ICAM-1 expression and sensitivity to LAK lysis suggest that interactions other than LFA-1/ICAM-1 conjugation may be more central to the processes involved.

Antibodies, Monoclonal↗
PubMed1992

Synergistic antitumor interactions between newly synthesized ruthenium complexes and cytokines in human colon carcinoma cell lines.

The purpose of these studies was to assess the antiproliferative properties of newly synthesized, heterocyclic ruthenium complexes alone and in combination with cytokines (tumor necrosis factor-alpha, interferon alfa, beta, and gamma) against various human colon carcinoma cell lines. To determine whether any of these ruthenium compounds possesses antitumor activity and reveals synergistic interaction with cytokines six new ruthenium complexes were studied. All six compounds exerted dose-dependent antitumor effects in all colon cancer cell lines tested. The most effective compounds were trans-indazolium[tetrachloro(2H-indazole)ruthenate (III, N1)] and trans-indazolium[tetrachlorobis(1 H-indazole)ruthenate (III, N2)]. Interferon alfa, beta, and gamma as well as tumor necrosis factor-alpha exerted only minimal antiproliferative effects in colon carcinoma cell lines. The data were further analyzed to determine whether preincubation with cytokines altered sensitivity of the cells to synergistically potentiating growth-inhibitory effects. Although simultaneous incubation of ruthenium complexes and interferon did not result in synergistic or additive interactions, 24-hour preincubation with interferon alfa, beta, and gamma significantly enhanced antitumor activity. We conclude from these data that two of six newly synthesized ruthenium complexes possess antiproliferative activity against a panel of human colon carcinoma cell lines. Moreover, biological modulation with interferon using 24-hour preincubation resulted in synergistic interactions. We are planning a phase I trial, since antitumor activity of these ruthenium compounds has been demonstrated in vitro and in vivo, and toxicity as well as stability data are now available.

Carcinoma↗
PubMed1992

The clinical application of the interferons: a review. NSW Therapeutic Assessment Group.

OBJECTIVES: To review the clinical information on the use of alpha, beta and gamma interferons and to classify the use of alpha interferons in Australia according to approved indications, indications for which there is good supporting evidence and indications where therapy is under investigation; and to estimate the cost of therapy with alpha interferons in New South Wales in 1991. DATA SOURCES: Data were obtained from computerised literature searches. DATA EXTRACTION: A position paper was drafted on behalf of the NSW Therapeutic Assessment Group (NSWTAG). This was circulated to clinicians identified as having a particular interest in the use of the interferons in major NSW teaching hospitals, for comment and amendment where necessary. CONCLUSIONS: Two forms of alpha interferon, interferon alfa-2b and interferon alfa-2a have been approved for use in Australia, interferon alfa-2b for use in the management of hairy cell leukaemia and condylomata acuminata and interferon alfa-2a for use in the management of hairy cell leukaemia and human immunodeficiency virus (HIV) related Kaposi's sarcoma. Applications have been lodged for the use of interferon alfa-2b in HIV related Kaposi's sarcoma, cutaneous basal cell carcinoma and hepatitis B and C and for the use of interferon alfa-2a in the management of hepatitis B, cutaneous T-cell lymphoma and metastatic renal cancer. Interferon alfa-n1 is not available in Australia except for use in a clinical trial in patients who are HIV seropositive. The use of the alpha interferons is currently under investigation in a wide variety of other diseases, with the likelihood that other indications will soon be established. However, the alpha interferons are generally not regarded as first line agents. Beta and gamma interferons have been studied less intensively than the alpha interferons, but it is likely that selected applications for their use will also be defined with the passage of time.

Australia↗
PubMed1992

[Role of interferon in the treatment of renal cancer in adults].

Alpha interferon is effective in the treatment of metastatic renal cell cancer. To obtain a maximal efficacy, alpha interferon should be used at a dose of 10 MU/m2, or 18 MU total dose, given daily or three times a week. At such doses interferon produces flu-like symptoms and severe asthenia and thus should be proposed only to patients who have a good performance status. The response rate is low, in the order of 15-20%, and the median remission duration is short (6-10 months). However a few patients experience very durable remissions, sometimes for more than 5 years. The response rate may possibly be improved to 20% to 35% by combining interferon alpha with antineoplastic agents or to other cytokines, namely interleukin 2. Finally because of its supposed mechanisms of action-direct tumor growth inhibition and enhancement of the host's immune defenses--interferon may be of benefit in the adjuvant setting.

Adult↗
PubMed1992

Elevated interleukin-6 and gamma-globulin during interferon therapy of hepatitis B.

A 49-yr-old man with chronic hepatitis B manifested hypergammaglobulinemia, lymphadenopathy, and a high serum interleukin-6 level following treatment with recombinant human alpha-interferon. One month later, when the patient was treated with natural beta-interferon, serum levels of interleukin-6 and gamma-globulin increased again. The serum gamma-globulin decreased to the pretreatment level after discontinuation of interferon therapy. The serum alanine aminotransferase level remained normal for 6 months. In this case, hypergammaglobulinemia and lymphadenopathy, as well as the elevated serum interleukin-6 level, were considered to be signs of highly enhanced humoral immunity related to alpha- and beta-interferon therapy.

Alanine Transaminase↗
PubMedDate not supplied

Natural killer cell activity against cultured melanoma cells: a dye-reduction technique with studies on augmented activity by interferon subtypes.

We assessed natural killer (NK) cell activity against cultured melanoma cells using a novel method, with observations on the comparative effects of interferons (IFNs) in NK-stimulating and anti-proliferative assays. Since the tumour cells tested were adherent, a semi-automated colorimetric MTT dye reduction assay was developed to assess NK activity. The three adherent human melanoma cell lines Sk-Mel-28, MM418 and MM96 were shown to be suitable targets for determining NK activity. Also, these were representative of the range of sensitivities of melanoma cells to the anti-proliferative action of type 1 IFNs. The dose-dependent stimulation of NK activity by type 1 IFNs was confirmed in this alternative assay system. IFN-alpha 2b and IFN-beta ser had equivalent stimulatory activities, and IFN-alpha 4 proved less effective, as with assays using the classical K562 system. Augmented NK cytotoxicity did not correlate with anti-proliferative effects of IFN. In anti-proliferative assays, the hierarchy of activity is IFN-beta greater than IFN-alpha 2 greater than IFN-alpha 4, whereas, in the NK augmentation assay IFN-beta and IFN-alpha 2 were of equivalent activity. Interestingly, MM96 was the cell line most resistant to the direct anti-proliferative action of IFN, yet it was the most susceptible of the melanoma cell lines to cytotoxicity by NK cells, whether stimulated or unstimulated by IFN.

Cytotoxicity, Immunologic↗
PubMed1992

Correlation between interferon (IFN) alpha resistance and deletion of the IFN alpha/beta genes in acute leukemia cell lines suggests selection against the IFN system.

Homozygous and hemizygous deletions of the interferon A (IFNA) and IFNB genes have been frequently observed in acute leukemia cell lines, primary acute leukemia cases, and gliomas. Because IFNs have an antiproliferative effect, selection against the IFN alpha/beta system could play a role or accompany the development of the malignant phenotype. Although the deletion of the IFNA/B genes could interrupt an autocrine loop that controls cell proliferation, cells would still respond to exogenous IFN alpha/beta and, thus, lesions at the receptor or signal transduction level should also be present to render cells resistant to exogenous IFN alpha/beta. To test if selection against the IFN system was operating in acute leukemias, the sensitivity to the antiproliferative effect of IFN alpha 2 was studied in acute leukemia cell lines with and without alterations of the IFNA/B genes. We found that 10 of 11 acute leukemia cell lines with alterations of the IFNA/B genes were resistant to the antiproliferative effect of IFN alpha 2, whereas only two of eight cell lines with normal IFNA/B genes were IFN-resistant. We then examined the possibility that an alteration of the receptor expression could account for the lack of response to IFN alpha 2. No significant alteration in the expression or structure of the IFN alpha receptor was observed. We also studied the downmodulation of the alpha subunit of the IFN alpha receptor upon IFN alpha 2 binding. One cell line with deletion of the IFNA/B genes showed impaired downmodulation of the IFN alpha receptor. The data presented here suggest that selection against the IFN alpha/beta system could play a role or accompany the development of the malignant phenotype.

Acute Disease↗
PubMedDate not supplied

The effects of interferon-alpha/beta in a model of rat heart transplantation.

Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.

Animals↗
PubMed1992

Variations of lymphocyte sub-populations in vulvar condylomata during therapy with beta-interferon.

Several experiences induced us to consider genital HPV infection as an expression of a local immunodeficiency. The aim of our study was to research the effect of immunotherapy on the lymphocyte subpopulations and Langerhans cells in vulvar condyloma. Twenty women with persistent vulvar condylomata, treated with 2,000,000 IU/die of beta-interferon for 15 days, were submitted to vulvar biopsy before and 2-5 months after medical treatment. The frozen sections obtained were assayed with the following monoclonal antibodies: OKT4 (T helper lymphocytes), OKT8 (T suppressor lymphocytes), OKB7 (B lymphocytes) and S-100 protein (Langerhans cells). Using a morphometric evaluation, the average number of both intraepithelial and stromal lymphocyte subsets and of the intraepithelial Langerhans cells was assessed. In all the biopsies preceding the medical treatment we found a low number of T helper lymphocytes both in the epithelium and stroma, with inversion of T4/T8 lymphocyte ratio and rare presence of Langerhans cells. In patients with a good therapeutic response (50-100% of condyloma reduction) we observed an increase in intraepithelial T4 lymphocytes and a decrease in both intraepithelial and stromal T8 lymphocytes. In cases with persistent disease after therapy, the histological pattern was similar to that observed in the first biopsy, with the exception of a significant increase in the average number of Langerhans cells. Our data correlate the clinical response to the immunotherapy with the histology of lymphocyte subsets in the vulvar condylomata. The increase in Langerhans cells observed in patients with negative response may be interpreted with a probable inability of these cells to promote the immune reaction.

Adult↗
PubMed1992

[Detection of the deletion of interferon-alpha and beta genes in lymphoblastoid cells by PCR].

The HuIFN-alpha and beta genes were examined by the PCR method in the 11 human lymphoblastoid cell lines. The results showed that the homozygous deletion of HuIFN-alpha and beta genes was detected in 5 of 11 cell lines and in 5 of 11 cell lines, respectively. The deletions of both the HuIFN-alpha and beta genes were observed in 4 of 11 cell lines. One T cell leukemia cell line deleted only HuIFN-alpha gene, while the other T cell leukemia line deleted only HuIFN-beta gene. This suggests that the deletions of HuIFN-alpha and beta genes may be related the development of leukemia or lymphoma.

Burkitt Lymphoma↗
PubMed1992

Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes.

The promoter regions of many interferon-inducible genes share a short DNA sequence motif, termed the interferon consensus sequence (ICS) to which several regulatory proteins bind. A murine cDNA which encodes an ICS binding protein has been reported (M-ICSBP). The cloning of the human homologue of ICSBP (H-ICSBP) is described. H-ICSBP shares high sequence homology with its murine cognate. The derived sequence of H-ICSBP reveals restricted homology within the first 120 amino acids to three other interferon regulatory factors, IRF-1, IRF-2, and ISGF3 gamma. Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS, indicating that at least part of the DNA binding domain is located within the well conserved amino terminus. H-ICSBP is expressed exclusively in cell lines of hematopoietic origin. The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. Furthermore, either interferon-gamma (IFN-gamma) or IFN-beta can alleviate the repression mediated by ICSBP. Therefore, ICSBP may be involved in maintaining submaximal transcriptional activity of IFN-inducible genes in hematopoietic cells. IFN treatment would then alleviate repression allowing maximal transcriptional activity of these genes.

Amino Acid Sequence↗
PubMed1992

Interferon regulatory factor-1 (IRF-1) activates the synthetic IRF-1-responsive sequence (GAAAGT)4 in Saccharomyces cerevisiae.

In appropriate mammalian cells, interferon regulatory factor-1 (IRF-1) can activate the virus-responsive element of the IFN-beta promoter (VRE beta") or the synthetic oligonucleotide (GAAAGT)4. The latter contains two copies of the functional equivalent of PRDI, one of the regulatory domains of VRE beta". We prepared yeast strains containing an IRF-1 expression plasmid under the control of the galactose-inducible Gal1 promoter and a reporter plasmid with either (GAAAGT)4, VRE beta", or other test sequences placed upstream of a minimal promoter linked to the beta-galactosidase coding sequence. Upon induction of IRF-1 expression, the (GAAAGT)4-containing promoter was activated, but VRE beta" and all other sequences tested were inactive. Our results showed that IRF-1 belongs to a class of higher eukaryotic transcription factors that can interact with the yeast transcriptional machinery. Our findings also raised the question why the duplicate PRDI-like sequences in (GAAAGT)4 can be activated by IRF-1 synthesized in yeast, but not VRE beta", which also contains at least two PRDI-like sequences.

Base Sequence↗
PubMed1992

Variations of lymphocyte sub-populations in vulvar condylomata during therapy with beta-interferon.

Several experiences induced us to consider genital HPV infection as an expression of a local immunodeficiency. The aim of our study was to research the effect of immunotherapy on the lymphocyte subpopulations and Langerhans cells in vulvar condyloma. Twenty women with persistent vulvar condylomata, treated with 2,000,000 IU/die of beta-interferon for 15 days, were submitted to vulvar biopsy before and 2-5 months after medical treatment. The frozen sections obtained were assayed with the following monoclonal antibodies: OKT 4 (T helper lymphocytes), OKT 8 (T suppressor lymphocytes), OKB 7 (B lymphocytes) and S-100 protein (Langerhans cells). Using a morphometric evaluation, the average number of both intraepithelial and stromal lymphocyte subsets and of the intraepithelial Langerhans cells was assessed. In all the biopsies preceeding the medical treatment we found a low number of T helper lymphocytes both in the epithelium and stroma, with inversion of T4/T8 lymphocyte ratio and rare presence of Langerhans cells. In patients with a good therapeutic response (50-100% of condyloma reduction) we observed an increase in intraepithelial T4 lymphocytes and a decrease in both intraepithelial and stromal T8 lymphocytes. In cases with persistent disease after therapy, the histological pattern was similar to that observed in the first biopsy, with the exception of a significant increase in the average number of Langerhans cells. Our data correlate the clinical response to the immunotherapy with the histology of lymphocyte subsets in the vulvar condylomata. The increase in Langerhans cells observed in patients with negative response may be interpreted with a probable inability of these cells to promote the immune reaction.

Adult↗