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At least 811 records · Page 45Linked to original sources
PubMed1997

Comparison of the effects of interleukin-1 alpha, interleukin-1 beta and interferon-gamma-inducing factor on the production of interferon-gamma by natural killer.

Interferon-gamma inducing factor (IGIF) is a recently identified cytokine which stimulates the production of interferon-gamma (IFN-gamma) by T cells and enhances natural killer (NK) cell cytolytic activity. Protein fold recognition, structure prediction and comparative modeling have revealed that IGIF is a member of the interleukin (IL)-1 cytokine family and has prompted the designation IL-1 gamma. Here we report functional similarities between members of the IL-1 family by comparing the effects of IL-1 alpha, IL-1 beta and IGIF on NK cell production of IFN-gamma. All three IL-1 types enhanced NK cell production of IFN-gamma when induced by IL-2 or IL-12, although at high concentrations (> 10 ng/ml), IGIF was five- to tenfold more potent than IL-1 alpha or IL-1 beta. This effect correlated with enhanced levels of mRNA for IFN-gamma when NK cells were stimulated with IGIF plus IL-12. In contrast to IL-12 and IL-2, the ability of IGIF to stimulate NK cell production of IFN-gamma was not increased by IL-1 alpha or IL-1 beta. The ability of IGIF to enhance IFN-gamma production was independent of the type I and type II IL-1 receptors or the IL-1R accessory protein. Together, these results identify IGIF as a potent stimulator of NK cell production of IFN-gamma and demonstrate that the effect of IGIF on NK cell production of IFN-gamma is similar to that of IL-1 alpha and IL-1 beta but distinct from that of IL-12.

Adjuvants, Immunologic↗
PubMed1998

Lymphoblastoid interferon alfa-n1 improves the long-term response to a 6-month course of treatment in chronic hepatitis C compared with recombinant interferon alfa-2b: results of an international randomized controlled trial. Clinical Advisory Group for the Hepatitis C Comparative Study.

The aim of this study was to compare the short-term and long-term efficacy and safety of lymphoblastoid interferon with a recombinant interferon alfa (IFN-alpha) in a 24-week treatment course for chronic hepatitis C. One thousand seventy-one patients with chronic hepatitis C were randomized to receive lymphoblastoid IFN-alpha n1 or recombinant IFN-alpha2b at the same dosing regimen, 3 million units administered subcutaneously three times a week for 24 weeks. Hepatitis C viral (HCV) genotype (by line probe assay) was determined at baseline, and serum HCV RNA level (by quantitative reverse-transcriptase polymerase chain reaction) was measured at baseline and weeks 24, 48, and 72. Primary end points were normalization of serum alanine aminotransferase (ALT) levels at end of therapy (week 24) and sustained ALT normalization at weeks 48 and 72. Secondary end points were nondetectability of serum HCV RNA at 24, 48, and 72 weeks, and histological improvement at weeks 24 and 72. The two treatment groups were similar with respect to demographic, clinical, and histological variables (10% had cirrhosis at entry), baseline serum HCV RNA levels, and distribution of HCV genotypes. Intent-to-treat analysis showed that ALT response at end of treatment was 35.3% for IFN-alpha n1 and 37.9% for IFN-alpha2b (P = .38). Histological improvement and nondetectability of HCV RNA were also similar between the two treatment groups at the end of treatment, as were the type and frequency of reported adverse experiences. Among treatment responders, post-treatment relapse was significantly less frequent with IFN-alpha n1 than with IFN-alpha2b. Thus, sustained ALT responses (SR) to IFN-alpha n1 were significantly more frequent than SR to IFN-alpha2b (12.0% vs. 7.6% at 48 weeks, P = .02; 10.3% vs. 6.7% at 72 weeks, P = .04). SR were associated with viral loss and histological improvement, and more patients treated with IFN-alpha n1 were HCV RNA negative at week 72 compared with patients treated with IFN-alpha2b (P = .03). SR at week 72 were two- to sixfold better with other HCV genotypes relative to type 1, but the improved long-term efficacy of IFN-alpha n1 compared with IFN-alpha2b was evident for all major HCV genotypes. It is concluded that IFN-alpha n1 and IFN-alpha2b have similar end-of-treatment response rates and safety profiles but the sustained response rate is higher with IFN-alpha n1. SR to IFN-alpha treatment are associated with clearance of HCV RNA, and histological improvement was maximal in patients who exhibited sustained ALT normalization and clearance of HCV RNA.

Adolescent↗
PubMed1998

Early hepatitis C virus-RNA responses predict interferon treatment outcomes in chronic hepatitis C. The Consensus Interferon Study Group.

In previous studies employing interferons (IFNs) in the treatment of chronic hepatitis C, there have been few reliable predictors of sustained responses. We retrospectively evaluated the predictive value of hepatitis C virus (HCV)-RNA measurements in the first few months during consensus interferon (CIFN) treatment using a sensitive reverse-transcriptase polymerase chain reaction assay to determine sustained responses. Data from two large treatment trials, one of IFN-naive patients and one of retreated relapsers and nonresponders, were used, including serum samples at 2-week intervals in the naive study and 8-week intervals in the retreatment study. Patients received initial CIFN (9 microgram) treatment for 6 months and were assessed 6 months after treatment. There were 28 sustained viral responders of 232 CIFN-treated patients. Of the sustained responders, 48% had already cleared HCV RNA from serum (<100 copies/mL) by week 2, 78% by week 4, 81% by week 6, and 96% by week 12. Patients with early HCV-RNA clearance were more likely to have sustained responses than those who responded later. Early clearance of HCV from serum was also associated with greater likelihood of a sustained response to 48 weeks of retreatment with 15 microgram CIFN. Ninety-five percent of the sustained responders were HCV-RNA-negative by week 8 of retreatment. Early assessment of HCV RNA may help in the prediction of sustained responses to IFN and allow the value of continued treatment to be determined early in the course of IFN therapy.

Antiviral Agents↗
PubMed1991

Modulation of tumoricidal activity, induced in bone-marrow-derived mononuclear phagocytes by interferon gamma or Corynebacterium parvum, by interferon beta, tumor necrosis factor, prostaglandin E2, and transforming growth factor beta.

Among a series of agents, including various interleukins and growth factors, only interferon gamma (IFN gamma) and heat-killed Corynebacterium parvum (CP) organisms were able to elicit, within 24 hr, tumoricidal activity in bone-marrow-derived mononuclear (BMM) phagocytes. In subsequent experiments, the abilities of interferon beta (IFN beta), tumor necrosis factor alpha (TNF alpha), prostaglandin E2 (PGE2), and transforming growth factor beta (TFG beta), alone or in combinations of 2, to modulate tumoricidal activity triggered in BMM phagocytes by IFN gamma or CP, were compared. In concentrations secreted by macrophages under physiological conditions, these agents proved potent in modulating induction and/or expression of tumoricidal activity. However, their ability to interfere with tumoricidal activity varied considerably, depending on the extent of macrophage differentiation and/or functional responsiveness, the pathway of macrophage activation, the type, concentration and combination of the macrophage secretory molecules, and on whether the agents were present during induction and expression or only during expression of tumoricidal activity. In showing that IFN beta and TNF alpha were mostly enhancing and TGF beta mostly suppressive, whereas PGE2 suppressed induction but enhanced expression of tumoricidal activity, our findings provide further support for the concept that these macrophage-derived molecules have a key role in autocrine regulation of macrophage functional activities.

Animals↗
PubMed1990

Synergistic interaction between interferon-alpha and interferon-gamma through induced synthesis of one subunit of the transcription factor ISGF3.

Interferon-alpha (IFN alpha) and interferon-gamma (IFN gamma) each induce in susceptible target cells a state of resistance to viral replication and reduced cellular proliferation, presumably through different mechanisms: these two polypeptides are unrelated by primary sequence and act through distinct cell-surface receptors to induce expression of largely non-overlapping sets of genes. However, acting in concert, they can produce synergistic interactions leading to mutual reinforcement of the physiological response. In HeLa cells, this synergistic response was initiated by cooperative induction of IFN alpha stimulated genes (ISGs). These normally quiescent genes were rapidly induced to high rates of transcription following exposure of cells to IFN alpha. Although they were only negligibly responsive to IFN gamma, combined treatment of cells with IFN gamma followed by IFN alpha resulted in an approximately 10-fold increase in ISG transcription. ISG transcription is dependent upon ISGF3, a positive transcription factor specific for a cis-acting regulatory element in ISG promoters. IFN gamma treatment induced increased synthesis of latent ISGF3, which was subsequently activated in response to IFN alpha to form approximately 10-fold higher levels than detected in cells treated with IFN alpha alone. ISGF3 is composed of two distinct polypeptide components, synthesis of one of which was induced by IFN gamma, increasing its cellular abundance from limiting concentrations to a level which allowed formation of at least 10 times as much active ISGF3. Cell lines vary in their constitutive levels of the inducible component of ISGF3 and in the ability of IFNs to increase its synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Nucleus↗
PubMed1994

Mice devoid of interferon regulatory factor 1 (IRF-1) show normal expression of type I interferon genes.

The transcription factor interferon regulatory factor 1 (IRF-1) binds tightly to the interferon (IFN)-beta promoter and has been implicated in the induction of type I IFNs. We generated mice devoid of functional IRF-1 by targeted gene disruption. As reported by others, IRF-1-deficient mice showed a discrete phenotype: the CD4/CD8 ratio was increased and IFN-gamma-induced levels of macrophage iNO synthase mRNA were strongly diminished. However, type I IFN induction in vivo by virus or double-stranded RNA was unimpaired, as evidenced by serum IFN titers and IFN mRNA levels in spleen, liver and lung. There was also no impairment in the response of type I IFN-inducible genes. Therefore, IRF-1 is not essential for these processes in vivo.

Animals↗
PubMed2002

Interferon regulatory factor-1, interferon-beta, and reovirus-induced myocarditis.

Viral myocarditis is an important human disease, and reovirus-induced myocarditis in mice provides an excellent model to study direct viral damage to the heart. Previously, we showed that reovirus induction of and sensitivity to interferon-beta (IFN-beta) is an important determinant of viral pathogenicity in the heart and that the transcription factor interferon regulatory factor-3 (IRF-3) is required for reovirus induction of IFN-beta in primary cardiac myocyte cultures. Given several lines of evidence suggesting a possible distinctive environment for IRFs in the heart, we have now focused on IRF-1. Previous studies demonstrated that viruses, double-stranded-RNA (dsRNA), and IFN-alpha/beta can each induce IRF-1 and that IRF-1 plays a role in dsRNA, but perhaps not viral, induction of IFN-alpha/beta. Importantly, none of these studies used a virus with a dsRNA genome (such as reovirus), none of them used a highly differentiated nonlymphoid cell type, and none of them addressed whether viral induction of IRF-1 is direct or is mediated through viral induction of IFN-beta. Indeed, as recently as this year it has been assumed that viral induction of IRF-1 is direct. Here, we found that reovirus induced IRF-1 in primary cardiac myocyte cultures, but that IRF-1 was not required for reovirus induction of IFN-beta. Surprisingly, we found that reovirus failed to induce IRF-1 in the absence of the IFN-alpha/beta response. This provides the first evidence that viruses may not induce IRF-1 directly. Finally, nonmyocarditic reovirus strains induced more cardiac lesions in mice deficient for IRF-1 than they did in wildtype mice, directly demonstrating a protective role for IRF-1. Together, the results indicate that while IRF-1 is downstream of the IFN-beta response, it plays an important protective role against viral myocarditis.

Animals↗
PubMed1988

Effects of scheduling and ascites-associated macrophages on combined antiproliferative activity of alpha-2b interferon and gamma-interferon in a clonogenic assay.

Effects of combination treatment with human recombinant alpha-2b interferon (IFN-alpha 2b) and gamma interferon (IFN-gamma) and sequencing of the combination on colony formation of human tumor cells were studied in a human tumor clonogenic assay (HTCA) with or without ascites-associated macrophages (AAM). Five different human tumor cell lines were studied. Three of the five cell lines (ovarian cancer cell line BG-1, cervical cancer cell line ME-180, and melanoma cell line SK-MEL 28) were sensitive to both IFNs. Cervical cancer cell line CaSki was sensitive to IFN-alpha 2b but resistant to IFN-gamma. Endometrial cancer cell line HEC-1A was resistant to both IFNs. Synergistic interaction was observed in BG-1 and SK-MEL 28 with a combination of the IFNs. ME-180 did not exhibit a positive interaction, in spite of its sensitivity to each IFN. CaSki and HEC-1A also did not exhibit a positive combined interaction at clinically achievable concentrations. One sequential combination method (method 1: IFN-alpha 2b----IFN gamma with a 24-h interval) resulted in a similar antitumor effect as the simultaneous combination. A reversed sequential method (method 2: IFN-gamma----IFN-alpha 2b with a 24-h interval) was less effective in three of the five cell lines. In BG-1, AAM enclosed in the lower layer markedly enhanced the antitumor effect of combined IFNs as well as each IFN alone. The antitumor effect with method 1 was significantly greater than that achieved with simultaneous combination or combination according to method 2 in the presence of AAM (P less than 0.01). These results suggest that (1) a synergistic antitumor effect of IFN-alpha 2b and IFN gamma is demonstrable in selected types of tumors, depending upon the sensitivity of each tumor cell line to both IFNs; (2) optimal scheduling for the direct antitumor effect of combined IFNs seems to be long-term exposure of cells to the IFN, the cells being treated with both IFNs either simultaneously or sequentially (IFN-alpha 2b preceding IFN-gamma); and (3) AAM potentiate the antitumor effect of IFNs either alone or in combination. Finally, IFN-alpha 2b may have some priming effects for the indirect effect of IFN gamma mediated through AAM in certain tumor cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Differential sensitivity of renal cell carcinoma xenografts towards therapy with interferon-alpha, interferon-gamma, tumor necrosis factor and their combinations.

Whereas cytokine therapy has proven efficacy in the treatment of metastatic renal cell carcinoma (RCC), many questions regarding the use of these drugs remain unanswered. In the present study we evaluated the antiproliferative effects of human recombinant alpha-interferon (IFN), gamma-interferon and tumor necrosis factor-alpha (TNF) on eight human RCC xenografts. In particular, the importance of the administration route, dosage and tumor load was investigated. Response to the cytokines differed widely amongst the different tumors. Of three tested routes of administration (i.v., i.p. and s.c. peritumoral), only the s.c. peritumoral route was effective against tumor growth. After 6 weeks of therapy consisting of 150 or 1,500 units IFN/g given s.c. peritumorally three times a week or 30,000 units TNF/g given five times a week, alpha-IFN treatment resulted in 2%-100% growth inhibition; gamma-IFN, in 7%-80%; and TNF, in 35%-75% as compared with the untreated control. Growth of five of eight tumor lines could be inhibited completely by combinations of IFN and TNF, whereby the tumor dimensions at the beginning of therapy were decisive for the results. In some cases IFNs had optimal doses; however, the antitumor effects of TNF were always dose-dependent. Our studies indicate that the doses at which the optimal direct effects of cytokines are measured are critically dependent on the tumor treated. Although direct effects are only one part of the mode of action of cytokines, our results indicate that dosage of cytokines may need individualisation.

Animals↗
PubMed1986

Enhanced production of gamma-interferon by therapy with parenteral OK-432 and alpha-interferon in patients with head and neck cancer.

Although the drug OK-432 can induce the release of gamma-interferon (IFN-gamma), the serum concentrations of IFN-gamma produced are very low. We studied the effects of combining OK-432 with alpha-interferon (IFN-alpha) on the endogenous production of IFN and the postoperative courses of patients with oral cavity cancers. Forty patients operated on for head and neck cancers were studied. Each patient was given an injection of OK-432 1 week after surgery. Between 10 and 14 days later, a combination of OK-432 and IFN-alpha was given to assess the effects of the concomitant use of IFN-alpha on IFN production. In 18 of the 30 patients given a large dose of IFN-alpha (3 or 5 X 10(6) IU/mg protein), IFN production induced by OK-432 was enhanced. A small dose of IFN-alpha (7 X 10(3) IU) did not enhance the action of OK-432. OK-432 also induced the release of both endogenous IFN-gamma and IFN-alpha, and the production of both types of IFN was enhanced by the concomitant administration of parenteral IFN-alpha. Next, 50 patients operated on for oral cavity cancers were given OK-432 or a combination of OK-432 and IFN-alpha for 4 months, and their postoperative courses were followed for 2-5 years. The clinical courses were better in the combined therapy group than in the group given OK-432 alone.

Biological Products↗
PubMed1992

Effects of tumor necrosis factor alpha, interferon alpha and interferon gamma on non-lymphoid leukemia cell lines: growth inhibition, differentiation induction and drug sensitivity modulation.

The potential role of tumor necrosis factor alpha (TNF alpha), interferon alpha (IFN alpha) and interferon gamma (IFN gamma) in the therapy of non-lymphoid leukemia was studied in ten non-lymphoid leukemia cell lines. All three cytokines tested inhibited the growth of the cell lines. However, a high degree of variability in susceptibility to cytotoxic/cytostatic effect of the cytokines was found among individual cell lines. Some cell lines were sensitive to the antiproliferative action of only one of the cytokines tested, but were resistant to the others. Combinations of two cytokines had additive or synergistic effects and inhibited cell growth to a greater extent than did the individual cytokines alone. In addition to the growth-inhibitory effect, the cytokines induced an apparent cell differentiation. The differentiation of the two most sensitive cell lines, EoL-1 and PL-21, was confirmed using the nitroblue tetrazolium reduction test, by changes in cell morphology, immunophenotype marker profiles and by changes in c-myb expression. Furthermore, we showed that even in the cell lines relatively resistant to the antiproliferative effect of cytokines, such as cell line KCL-22, the inhibition of cell growth could be markedly increased with the DNA-topoisomerase-II-targeted drug, doxorubicin. Our data thus suggest that TNF alpha, IFN alpha and IFN gamma together have a potential role in the immunotherapy of non-lymphoid leukemia in terms of their antiproliferative action, and their ability to induce differentiation and to modulate drug sensitivity.

Cell Differentiation↗
PubMed1987

[Effectiveness of gamma interferon and alpha interferon in hairy cell leukemia].

Six patients with hairy-cell leukemia were treated with gamma-(IFN-gamma) and alpha-(IFN-alpha-2b) interferon; 3-35 months following splenectomy, treatment was started with 4 X 10(6) U/m2 IFN-gamma sc (iv) every second day for 9-35 weeks. Although the white blood cell counts decreased during therapy from 4.1-49 X 10(9)/l to 1.5-43 X 10(9)/l, no hematological or clinical improvement was obtained. Subsequently (interval 0-13 weeks), IFN-alpha-2b was given at an initial dose of 4 X 10(6) U/m2 sc every second day to all patients. After a treatment period corresponding to that of IFN-gamma administration, a significant hematological improvement was observed in five patients (one early death due to pulmonary embolism). At the last follow-up (9-14 months after start of treatment; maintenance therapy, 1 X 10(6) U every second day), these patients exhibited normal peripheral blood cell counts, and in bone marrow biopsy specimens a marked decrease of hairy cells was seen (1 CR, 3 PR, 1 MR). Adverse reactions including fever, headache, nausea, dryness of the mouth, myalgia, and fatigue did not significantly differ between the two interferon preparations. Whereas IFN-gamma is unlikely to have any significant impact on the course of hairy cell leukemia, IFN-alpha-2b does result in improvement of hematological values and well-being in almost all patients.

Adult↗
PubMed1992

Interferon-alpha, interferon-gamma and sizofiran in the adjuvant therapy in ovarian cancer--a preliminary trial.

The study included 24 cases of negative second-look laparotomy (SLL) after operation on ovarian cancer. 12 cases were treated with sizofiran and recombinant interferon-gamma before and after SLL and then with human lymphoblastoid interferon-alpha. The remaining 12 cases (controls) were followed up without any drug therapy after SLL. There were no recurrences in the treated group, but in 3 cases of the control group. Also significant difference in survival was noted in the treated group.

Adult↗
PubMed1991

Antiproliferative effects of natural human tumor necrosis factor-alpha, interferon-alpha, and interferon-gamma on human pancreatic carcinoma cell lines.

The antiproliferative effects of natural human tumor necrosis factor-alpha (nHuTNF-alpha), natural human interferon-alpha (nHuIFN-alpha), and natural human interferon-gamma (nHuIFN-gamma) were investigated in human pancreatic carcinoma cell lines. HuP-T3, HuP-T4, and BxPC-3 carcinoma cells exhibited mild growth inhibition after treatment with nHuTNF-alpha. HuP-T3, HuP-T4, MIA-PaCa-2, and BxPC-3 cells exhibited mild or marked growth inhibition after treatment with nHuIFN-alpha. Incubation with nHuIFN-gamma caused marked growth inhibition of HuP-T4 and BxPC-3 cells, whereas HuP-T1, HuP-T3, and MIA-PaCa-2 cells showed only mild growth inhibition with the same dose of nHuIFN-gamma. Combined nHuTNF-alpha and nHuIFN-alpha (1:1) demonstrated marked synergism in comparison with their effects as single agents on HuP-T1, HuP-T3, and MIA-PaCa-2 cells. The combination of nHuTNF-alpha and nHuIFN-gamma (100:1) also demonstrated a marked synergistic effect in comparison with these cytokines alone in four out of five pancreatic carcinoma cell lines (HuP-T1, HuP-T3, HuP-T4, and MIA-PaCa-2 cell lines). The marked increase in efficacy brought about by using combinations of cytokines may enable some improvement in the treatment of pancreatic carcinoma patients in the future.

Cell Line↗
PubMed2004

[Impact of immunochemotherapy on survival of patients with metastatic renal cell carcinoma. A retrospective study comparing interferon-alpha-2a/vinblastine versus interferon-alpha-2a/interleukin-2/5-fluorouracil].

The prognosis for patients with metastatic renal cell carcinoma (RCC) remains unsatisfactory to date. Combined immunochemotherapy (ICT) strives for a synergistic effect avoiding a substantial increase of therapy-related adverse events. The combination therapy regimes consisting of either interferon-alpha-2a/vinblastine (IFN-alpha2a/VBL) or interferon-alpha-2a/interleukin-2/5-fluorouracil (IFN-alpha2a/IL-2/5-FU) demonstrated objective remission rates, surpassing the results obtained with the administration of single immunotherapeutic agents. Despite the data from a recently published study, the role of these two therapy combinations did not seem clearly defined. Therefore, we compared the impact of IFN-alpha2a/VBL and IFN-alpha2a/IL-2/5-FU on remission and survival as well as the safety profile in a retrospective study in patients with metastatic RCC. In a retrospective single-center study, 105 patients with metastatic RCC having received treatment between 1992 and 2002 with either s.c. IFN-alpha2a/ i.v. VBL ( n=70, group 1) or s.c. IFN-alpha2a/ s.c. IL-2/ i.v. 5-FU ( n=35, group 2) were evaluated. At a median follow-up of 17 months, remission and survival rates as well as the toxicity profiles of the respective groups were documented and compared. The median age throughout the entire patient population was 61 years. Patients in the IFN-alpha2a/VBL group reached a median overall survival of 20 months compared to 17 months for the patients in the IFN-alpha2a/IL-2/5-FU population ( p=0.850). The objective response rate in the first patient group reached 25.7%, whereas the tumor remission rate of group 2 amounted to 22.9% ( p=0.680). Patients showing an objective response reached a significantly higher survival rate than patients without response reaction (median survival was 36 vs 10 months, p=0.0001). The incidence of each therapy-induced adverse event was higher throughout the second treatment group. These differences were significant with respect to flu-like symptoms (85.7 vs 57.1%, p=0.003), grade 3/4 elevations of liver enzymes (14.3 vs 1.4%, p=0.007), nausea/vomiting (74.3 vs 50%, p=0.017), the severity of erythemas (74.3 vs 10%, p<0.001), and patients with lung edema (17.1 vs 2.9%, p=0.009). Eight patients discontinued the ICT, two of whom died of a myocardial infarction.Despite an overall limited prognosis, patients showing a tumor remission seem to benefit from ICT in terms of overall survival. While both treatment options offer comparable remission and survival rates, the IFN-alpha2a/VBL regimen induces fewer adverse events than the treatment with IFN-alpha2a/IL-2/5-FU.

Adult↗
PubMed1986

Interferon alpha/beta selectively antagonises down-regulation of mannosyl-fucosyl receptors on activated macrophages by interferon gamma.

Previous reports have described synergism of various interferon preparations in anticellular and antiviral activity. We report that recombinant interferon (rIFN gamma) and IFN alpha/beta mediate distinct, antagonistic effects on expression of a lectin-like receptor for mannose and fucose (MFR) on mouse peritoneal macrophages (M phi). IFN gamma down-regulates MFR activity, a highly reproducible change in mouse M phi activated to secrete enhanced levels of o-2/H2o2. IFN alpha/beta enhances MFR activity and prevents the action of IFN gamma when added in combination. Antagonism is selective for this M phi activation marker and requires a minimum 4 h exposure period to rIFN gamma, during which IFN alpha/beta can prevent its action.

Animals↗
PubMed1983

Spontaneous production of interferon-gamma and acid-labile interferon-alpha by subpopulations of human mononuclear cells.

A low-density subpopulation of normal human peripheral blood mononuclear leukocytes obtained by percoll gradients was found to produce significant levels (up to 10,000 units/ml) of interferon in the absence of an external inducer. The interferon (IFN) was characterized as a mixture of IFN-gamma (immune) and a pH-sensitive IFN-alpha by neutralization with specific antibodies, by lability to low pH, and by cross-reactivity on bovine cells. Significant levels of IFN were obtained only at high (greater than or equal to 5 X 10(6) cells/ml) cell densities. These levels were not affected by the presence of small T lymphocytes and sharply decreased with cell dilution in a nonlinear fashion. A release of IFN in the absence of an external inducer, indicates additional physiological roles besides its involvement in pathological conditions.

Cells, Cultured↗
PubMed1996

Codeletion of the genes for p16INK4, methylthioadenosine phosphorylase, interferon-alpha1, interferon-beta1, and other 9p21 markers in human malignant cell lines.

In this study, 27 malignant cell lines, including leukemias, gliomas, and lung and bladder carcinomas were screened for homozygous deletions of the putative tumor suppressor gene p16 (MTS1/CDK4I/CDKN2) and other markers within the chromosome 9p21 region; these include the genes for interferon-alpha1 (IFNA1), interferon-beta1 (IFNB1), methylthioadenosine phosphorylase (MTAP), and two microsatellite markers, D9S171 and D9S169. The purpose of this study was to determine the incidence of codeletion of these markers. Screening for homozygous deletions was carried out using direct polymerase chain reaction of genomic DNA, or, in the case of MTAP, a functional enzyme assay. Of these cell lines, 14 (52%) were found to have homozygous deletions of the p16 gene. Two of the 14 p16-negative cell lines (14%) were found to have homozygous deletions within the p16 domain but but no other 9p21 marker. MTAP was codeleted in 12 of the 14 p16-negative cell lines (86%), whereas IFNA1 was codeleted with p16 in eight of these lines (57%); IFNB1 was codeleted in five (36%) of the p16-deleted cell lines. The D9S171 marker, which may lie greater than 3 cM centromeric to p16, is codeleted in three cell lines (21%); the D9S169 marker, which maps even further toward the centromere, was codeleted in only one cell line (7%). Loss of any 9p21 marker, e.g., MTAP or IFNA1, were invariable predictors of the loss of the p16 gene. In addition, loss of IFNA1 always predicted a loss of MTAP (eight of eight cell lines), although loss of MTAP did not always predict a loss of IFNA1 (four of 12 MTAP-deleted cell lines did not have homozygous deletions of IFNA1). Thus loss of nearby genes occurs in a high percentage of cell lines that bear homozygous deletions of the p16 locus. Codeletion of MTAP or IFN in p16-negative malignant cells is of interest, as loss of these genes may influence the biologic behavior of these cells and render them susceptible to certain therapeutic approaches.

Base Sequence↗