Showing papers on "Interferon published in 1989"
TL;DR: The effects of gamma IFN on monolayer barrier function were not duplicated by the cytokine interferon 1, interleukin 2, or tumor necrosis factor, and it is speculated that such products of activation of lymphoid cells might influence barrier function of intestinal, and perhaps other epithelia in disease states.
Abstract: Although epithelia, which often are in intimate contact with lymphoid cells, may bear receptors for various cytokines, it is unclear whether cytokines directly effect epithelial function. We examine the effects of the cytokine interferon (IFN) on barrier function of cultured monolayers of the T84 human intestinal epithelial cell line. Gamma IFN, in concentrations and exposures required to show its other biological effects, directly affects such monolayers. Monolayer resistance is substantially diminished by gamma IFN. Such effects were not due to cytotoxicity as judged morphologically and by LDH assays. Solute fluxes and dual Na+-mannitol flux analysis indicate that the resistance decrease is due to an effect of gamma IFN on tight junction permeability. The effects of gamma IFN on monolayer barrier function were not duplicated by the cytokines interleukin 1, interleukin 2, or tumor necrosis factor. We speculate that such products of activation of lymphoid cells might influence barrier function of intestinal, and perhaps other epithelia in disease states.
756 citations
TL;DR: The sequence of a cDNA clone encoding Bp50 was analyzed and an extensive homology with the nerve growth factor receptor was found, suggesting a role for the molecule in the development of carcinomas at sites of chronic inflammation.
Abstract: B cells and primary carcinomas express a surface molecule, Bp50 (CDw40), absent from other hematopoietic cells and from normal epithelium, and thought to play a regulatory role in B-cell maturation and epithelial neoplasia In this work the sequence of a cDNA clone encoding Bp50 was analyzed by a newly derived transition matrix method Among several interesting relationships with known receptors was found an extensive homology with the nerve growth factor receptor The mRNA is induced by gamma-interferon in both B cells and epithelial neoplasms, suggesting a role for the molecule in the development of carcinomas at sites of chronic inflammation
620 citations
TL;DR: It is suggested that this protein blocks the function of TNF by competing for TNF with the TNF receptor and not by interacting with the target cell.
521 citations
TL;DR: MHC-I expression on muscle fibers is necessary but not sufficient for TCMC in myopathy; that the biological significance of increased MHC- I expression in DM remains undefined; and that currently available and appropriately controlled immunocytochemical methods show no relationship between increased M HC-Iexpression on muscle fiber and local IFN synthesis by mononuclear cells.
336 citations
TL;DR: Human cells treated with interferon synthesize two proteins that exhibit high homology to murine Mx1 protein, which has previously been identified as the mediator ofinterferon-induced cellular resistance of mouse cells against influenza viruses.
Abstract: Human cells treated with interferon synthesize two proteins that exhibit high homology to murine Mx1 protein, which has previously been identified as the mediator of interferon-induced cellular resistance of mouse cells against influenza viruses. Using murine Mx1 cDNA as a hybridization probe, we have isolated cDNA clones originating from two distinct human Mx genes, designated MxA and MxB. In human fibroblasts, expression of MxA and MxB is strongly induced by alpha interferon (IFN-alpha), IFN-beta, Newcastle disease virus, and, to a much lesser extent, IFN-gamma, MxA and MxB proteins have molecular masses of 76 and 73 kilodaltons, respectively, and their sequences are 63% identical. A comparison of human and mouse Mx proteins revealed that human MxA and mouse Mx2 are the most closely related proteins, showing 77% sequence identity. Near their amino termini, human and mouse Mx proteins contain a block of 53 identical amino acids and additional regions of very high sequence similarity. These conserved sequences are also present in a double-stranded RNA-inducible fish gene, which suggests that they may constitute a functionally important domain of Mx proteins. In contrast to mouse Mx1 protein, which accumulates in the nuclei of IFN-treated mouse cells, the two human Mx proteins both accumulate in the cytoplasm of IFN-treated cells.
325 citations
TL;DR: A role for NF‐kappa B in the physiological activation of genes in non‐lymphoid cells is demonstrated, and induction by dsRNA provides a novel means for the post‐translational activation of NF‐ kappa B.
Abstract: The human beta-interferon promoter contains at least two positive acting domains (PRD I and PRD II). PRD I has been previously shown to stimulate basal transcription and to respond to induction by double-stranded RNA (dsRNA). Here we show that PRD II functions independently as a constitutive element that also responds to induction. A cellular factor that specifically binds to PRD II has been identified, and the levels of this factor increase markedly in extracts from cells treated with dsRNA. The inducible factor has a binding specificity that is indistinguishable from the transcription factor NF-kappa B. As has been shown for NF-kappa B, the PRD II-specific factor can be activated in uninduced extracts by treatment with detergent, suggesting that the inactive state is due to association with an inhibitory factor. Induction by dsRNA therefore provides a novel means for the post-translational activation of NF-kappa B. Potential binding sites for NF-kappa B are present in the 5' flanking regions of a number of genes involved in the immune response, several of which are inducible by dsRNA. These findings demonstrate a role for NF-kappa B in the physiological activation of genes in non-lymphoid cells.
279 citations
TL;DR: It appears that IRF-1 may be necessary but not sufficient for IFN-beta induction, and the ability of TNF and IL-1 to increase both IRf-1 and IFn-beta mRNAs may be responsible for some similarities in the actions of T NF, IL- 1, andThe IFNs.
Abstract: Nuclear protein IRF-1 (interferon regulatory factor 1) was earlier shown to bind to cis-acting regulatory elements present on interferon (IFN)-alpha/beta genes and some IFN-inducible genes. Here we show that in both human FS-4 and murine L929 cells, steady-state levels of IRF-1 mRNA were increased by treatment with tumor necrosis factor (TNF), interleukin 1 (IL-1), poly(I).poly(C), or IFN-beta. IRF-1 mRNA induction was also demonstrated in cells treated with calcium ionophore A23187 or with phorbol 12-myristate 13-acetate, but not with epidermal growth factor, dibutyryl-cAMP, or the adenylate cyclase activator forskolin. To determine whether stimulation of IRF-1 mRNA levels correlates with IFN-beta induction, we compared IRF-1 and IFN-beta mRNA levels in cells exposed to various stimuli. In L929 cells, treatment with poly(I).poly(C) under conditions that failed to induce significant levels of IFN-beta mRNA led to a very low induction of IRF-1 mRNA, but "priming" cells with IFN prior to the addition of poly(I).poly(C) greatly increased both IRF-1 and IFN-beta mRNAs. In FS-4 cells an increase in IFN-beta mRNA (examined by the polymerase chain reaction) was seen after treatment with TNF, IL-1, A23187, or poly(I).poly(C), but not with IFN-beta, epidermal growth factor, dibutyryl-cAMP, or forskolin. Thus, all treatments that increased steady-state levels of IFN-beta mRNA also enhanced IRF-1 mRNA levels. However, treatment with IFN-beta, which caused a marked stimulation in IRF-1 mRNA, failed to produce a detectable increase in IFN-beta mRNA. It appears that IRF-1 may be necessary but not sufficient for IFN-beta induction. The ability of TNF and IL-1 to increase both IRF-1 and IFN-beta mRNAs may be responsible for some similarities in the actions of TNF, IL-1, and the IFNs.
277 citations
TL;DR: The results suggest that chronic hepatitis B with anti‐HBe in serum differs from chronic hepatitis with HBeAg in both natural history and response to interferon, witheculiar features are the frequency of spontaneous remissions and a high frequency of reactivation after a response to Interferon.
233 citations
Journal Article•
222 citations
TL;DR: It is demonstrated that induction of indoleamine 2,3-dioxygenase is a common feature of interferon-gamma action, that the extent of this induction is influenced by extracellular L-tryptophan concentrations and that indoleamines 2, 3-Dioxy genase is the only enzyme in the formation of 3-hydroxyanthranilic acid from tryptophan which is regulated by interferons-Gamma.
194 citations
TL;DR: The results suggest that interferon alpha/beta exerted an antitumor effect in these tumor models by damaging tumor blood vessels, causing disruption of tumor blood flow, which led to ischemic tumor necrosis.
Abstract: DBA/2 mice were injected sc with cells from the highly malignant Friend erythroleukemia cell (FLC) 3Cl8 subline, which is resistant to mouse interferon alpha/beta, or with the ESb lymphoma. When interferon alpha/beta was injected intratumorally or peritumorally, tumor growth was markedly suppressed, and established vascularized tumor nodules became progressively necrotic. Tumor necrosis was of the coagulation type that usually results from deprivation of blood flow. Morphologic examination of approximately 1,000 blood vessel profiles and approximately 2,000 endothelial cells in 1-micron Epon sections of sc 3C18 FLC tumors showed that interferon treatment resulted in rapid and pronounced vascular endothelial cell damage that preceded tumor necrosis. No inflammatory cell infiltrate was observed. Our results suggest that interferon alpha/beta exerted an antitumor effect in these tumor models by damaging tumor blood vessels, causing disruption of tumor blood flow, which led to ischemic tumor necrosis.
TL;DR: Rec recombinant human granulocyte/macrophage colony-stimulating factor was administered to cancer patients to determine whether the cytotoxic and secretory activity of their blood monocytes could be enhanced, and data indicate that rGM-CSF can enhance both the number and the function of peripheral blood monocyte in vivo.
TL;DR: The results suggest a model for signal transduction in which latent E factor, located in the cytoplasm, is activated or released from an inhibitor very rapidly upon binding of IFN-alpha to its receptor.
Abstract: The highly conserved interferon (IFN)-stimulated regulatory elements of the human genes 6-16 and 9-27 bind to one or more proteins (E factor) detected in extracts of human Bristol 8 B cells or human foreskin fibroblast cells treated with IFN-alpha E factor is not detectable in extracts of untreated cells and appears in IFN-treated cells within less than 1 min in a form extractable with low salt and thus presumably not bound to DNA After a few more minutes, the level of this form decreases in parallel with the increase of a form extractable only with high salt and thus presumably bound to DNA Induction of E factor by IFN-alpha can occur in nuclei-free cytoplasts, whereas no E factor was detected in IFN-treated nucleoplasts Together, these results suggest a model for signal transduction in which latent E factor, located in the cytoplasm, is activated or released from an inhibitor very rapidly upon binding of IFN-alpha to its receptor Active E factor can then migrate to the nucleus, where it binds to the IFN-stimulated regulatory elements of IFN-regulated genes, activating their transcription
TL;DR: An RNase protection assay is used to demonstrate that IL-4 induces expression of germ-line gamma 1 transcripts in B cells within 4 hr of culture; induction is dose-dependent and is inhibited by interferon gamma, which strongly support the "accessibility" model for the regulation of isotype switching.
Abstract: Interleukin 4 (IL-4) induces the expression of IgG1 and IgE in lipopolysaccharide-stimulated B cells. Previous studies have suggested that heavy-chain class switching may be regulated by increasing the accessibility of specific switch regions to switch recombinases. In this study, we have used an RNase protection assay to demonstrate that IL-4 induces expression of germ-line gamma 1 transcripts in B cells within 4 hr of culture; induction is dose-dependent and is inhibited by interferon gamma. IL-4 alone is capable of inducing the expression of germ-line gamma 1 transcripts in small, resting B cells, but lipopolysaccharide enhances expression. The germ-line transcripts are the same size (1.8 and 3.4 kilobases) as the secreted and membrane forms of the functional gamma 1 mRNAs and presumably result from the splicing of an upstream switch-region exon(s) to the gamma 1 constant-region exon(s). These data strongly support the "accessibility" model for the regulation of isotype switching and suggest that lymphokines such as IL-4 may direct specific switch events by transcriptional activation of the corresponding switch regions.
TL;DR: Tumor cell-associated expression of multidrug resistance (MDR) was quantitated in 22 patients with DNA-aneuploid myeloma using 2-parameter flow cytometry with monoclonal antibody (MoAb) C-219 for the detection of cytoplasmic p-170 and propidium iodide for nuclear DNA content.
TL;DR: Significant indoleamine 2,3-dioxygenase activity was observed only in macrophages treated with IFN-gamma or combinedIFN-beta plus lipopolysaccharide, and resulted in greater than 50% of available tryptophan being catabolized in a 4-h period, which partially reversed the effect of IFN on the inhibition of C. psittaci replication.
Abstract: Interferon-γ (IFN-γ) previously has been shown to inhibit the replication of Chlamydia psittaci in epithelial cells by inducing indoleamine 2,3-dioxygenase, the enzyme that decyclizes tryptophan to N-formylkynurenine. The role of indoleamine 2,3-dioxygenase in IFN-mediated inhibition of C. psittaci in human macrophages has now been examined. Peripheral blood monocytes from normal donors were isolated and cultivated 10–14 days to allow differentiation to macrophages. Cells were then treated with either IFN-γ or IFN-β for 48 h before infection with sufficient C. psittaci to infect approximately 30% of the cells. Infected cells were incubated 24 h, at which time coverslips were fixed, stained with Giemsa, and examined for development of C. psittaci inclusions by light microscopy. Complete inhibition of inclusion development was observed with IFN-γ. In the absence of lipopolysaccharide, inhibition of C. psittaci by IFN-γ was variable; however, in the presence of lipopolysaccharide, IFN-γ also complet...
TL;DR: Stably introduced a human 2-5A synthetase cDNA into a human glioblastoma cell line (T98G) andConstitutive expression of the cDNA in these cells is associated with increased levels of resistance to infection by encephalomyocarditis virus.
Abstract: The interferon (IFN)-induced enzyme 2′,5′-oligoadeny late (2-5A) synthetase has been implicated in the development of antiviral activity in human and animal cells. However, its role in IFN...
TL;DR: Induction of GBP by gamma IFN is presumably mediated by a factor different from the recently described activator Interferon Stimulated Gene Factor 3 (ISGF3) because induction of this factor was not observed upon treatment of cells with Gamma IFN.
Abstract: Transcriptional regulation of the gene encoding a guanylate-binding protein (GBP) by the two interferon (IFN) types was studied. GBP gene transcription was regulated by alpha IFN in a manner identical to that of previously described IFN-stimulated genes (ISGs): rapid induction, without a need for protein synthesis, followed by a protein synthesis-dependent suppression of transcription to basal levels within 6 h. Transcriptional induction by gamma IFN was equally rapid and independent of ongoing protein synthesis but remained at elevated levels for greater than 24 h. Experiments employing combined treatments with IFNs of both types revealed that induction of the GBP gene by gamma IFN overrides the alpha IFN-induced active repression and reverses the alpha IFN-induced repressed state. Moreover, the alpha IFN-mediated repression of ISG54, a gene normally responsive to only alpha IFN, is also reversed by gamma IFN. Induction of GBP by gamma IFN is presumably mediated by a factor different from the recently described activator Interferon Stimulated Gene Factor 3 (ISGF3) because induction of this factor was not observed upon treatment of cells with gamma IFN. Finally, a complex set of reinforcing or synergistic effects were observed when induction of the GBP gene was evoked by a combined treatment with the two IFN types.
TL;DR: Experiments suggest that induction of IFN gene expression may be controlled in part by transcription regulatory proteins binding to an NF-kappa B-like site within the IFN-beta promoter.
Abstract: The relationship between transcription of alpha and beta interferon (IFN-alpha and IFN-beta) genes and the interaction of IFN promoter-binding transcription factors has been examined in monoblastoid U937 cells following priming with recombinant IFN-alpha 2 (rIFN-alpha 2) and Sendai virus induction. Pretreatment of U937 cells with rIFN-alpha 2 prior to Sendai virus infection increased the mRNA levels of IFN-alpha 1, IFN-alpha 2, and IFN-beta as well as the final yield of biologically active IFN. Analysis of nuclear protein-IFN promoter DNA interactions by electrophoretic mobility-shift assays demonstrated increased factor binding to IFN-alpha 1 and IFN-beta regulatory domains, although no new induction-specific complexes were identified. On the basis of competition electrophoretic mobility-shift assay results, factors interacting with the IFN-alpha 1 and IFN-beta promoters appear to be distinct DNA-binding proteins. U937 factor binding was localized to the P2 domain (-64 to -55) of the IFN-beta regulatory element, a sequence motif with 80% homology to the recognition site of transcription factor NF-kappa B. Protein-DNA interactions within the IFN-beta P2 domain were, in fact, specifically competed by either excess homologous P2 fragment or the human immunodeficiency virus enhancer element which contains two duplicated NF-kappa B recognition sites. Hybrid promoter-chloramphenicol acetyltransferase fusion plasmids, containing either the IFN-beta regulatory element or the human immunodeficiency virus enhancer element linked to the simian virus 40 promoter, were analyzed for virus and phorbol ester inducibility in epithelial and lymphoid cells, respectively. In the 293 cell line, both plasmids were constitutively expressed but not virus inducible, while in Jurkat cells, chloramphenicol acetyltransferase activity from these plasmids was induced by tumor-promoting agent treatment. These experiments suggest that induction of IFN gene expression may be controlled in part by transcription regulatory proteins binding to an NF-kappa B-like site within the IFN-beta promoter.
TL;DR: Results suggest that interferon can sensitize cells to FUra inhibition of thymidylate synthase by enhancing accumulation of FdUMP.
TL;DR: It is confirmed that oTP-1, which at days 15-17 of pregnancy is produced by a single embryo at more than 100 micrograms (greater than 1 million antiviral units) per day, is a functional IFN.
Abstract: Ovine trophoblast protein-1 (oTP-1), the major product secreted by the trophectoderm of the sheep conceptus between days 13 and 21 of pregnancy, is considered to mediate maternal recognition of pregnancy by maintaining the function of the corpus luteum. Its amino acid sequence has 40–55% identity with various mammalian interferons-α (IFN-α), and it has been shown to have antiviral activity. The present results confirm that oTP-1, which at days 15–17 of pregnancy is produced by a single embryo at more than 100 μg (>1 million antiviral units) per day, is a functional IFN. A preparation of purified oTP-1 was made. Its amino-terminal sequence suggested that it consisted of a single homogeneous protein, so that its antiviral activity probably was not due to a contaminant. In a cytopathic effect inhibition assay with GBK-2 bovine cells challenged with vesicular stomatitis, its specific activity was 1.3 × 107 end point units/mg protein. It also protected GBK-2 cells against four other viruses, and A549 ...
TL;DR: Tumour necrosis factor-alpha alone was ineffective in peripheral blood mononuclear cells and macrophages, but it significantly increased the action of all three interferon species on macrophage and fibroblasts.
Abstract: The capacity of recombinant interferon-alpha, -beta and -gamma, of bacterial lipopolysaccharide and of recombinant tumour necrosis factor-alpha to induce indoleamine 2,3-dioxygenase and synthesis of pteridines was studied in human peripheral blood mononuclear cells, human macrophages and normal dermal fibroblasts. The action of interferon-alpha and -beta on macrophages was supported by lymphocyte factors as indicated by the effect of these mediators in the absence or presence of lymphocytes. Tumour necrosis factor-alpha alone was ineffective in peripheral blood mononuclear cells and macrophages, but it significantly increased the action of all three interferon species on macrophages and fibroblasts. Lipopolysaccharide directly affected macrophages or dermal fibroblasts and enhanced the effect of interferon-gamma. However, in the presence of lymphocytes, the action of lipopolysaccharide was mediated via interferon-gamma.
TL;DR: This study clearly demonstrates effects of IFN-alpha 2 treatment on both the leukemic cells and on the nonleukemic components of the immune system in peripheral blood and whether IFn-alpha treatment will result in long-term beneficial effects in early stage CLL.
TL;DR: The purification of a host cell factor is reported that is capable of binding in vitro to an oligomerized form of the hexanucleotide sequence GAAACG, which is common to a variety of virus- and interferon-inducible genes.
Abstract: Expression of herpes simplex virus type 1 (HSVl) immediate early (IE) genes is activated by a polypeptide component of the mature virion termed viral protein 16 (VP16). Stimulation of IE expression by VP16 operates via two cis-regulatory sequences: TAATGARAT, and the purine-rich hexanucleotide sequence GCGGAA. VP16 does not bind directly to either of the IE cis-regulatory sequences. Rather, these elements appear to represent binding sites for host cell proteins. Herein, we report the purification of a host cell factor that binds to the GCGGAA motif. We show further that this factor is capable of binding in vitro to an oligomerized form of the hexanucleotide sequence GAAACG, which is common to a variety of virus- and interferon-inducible genes. The GAAACG repeats of interferon- and virus-inducible genes, and the GA-rich repeats of HSVl IE genes confer similar functional properties when appended to the promoter of a heterologous gene. These observations raise the possibility that HSVl may activate its IE genes in a manner that exploits one of the components used by mammalian cells to combat virus infection.
TL;DR: The data suggest that virus-trans-activated alpha 2-interferon synthesis can be used as a selective inhibitor of HIV replication.
Abstract: We have prepared stable cell lines, derived from Vero cells and A3.01 cells, that express a hybrid human alpha 2-interferon gene under control of the human immunodeficiency virus (HIV) long terminal repeat. These cells constitutively produced low levels (50-150 units/ml) of alpha 2-interferon. However, high levels of interferon (10(3) units/ml) could be induced upon trans-activation by the product of the tat gene (pIIIextatIII), and de novo infection by HIV resulted in a moderate increase (400 units/ml) in alpha 2-interferon synthesis. In contrast to the fully permissive HIV replication, in transfected Vero cells or infected A3.01 cells, the transcription and replication of HIV in Vero or A3.01 cells containing the HIV long terminal repeat--alpha 2-interferon hybrid gene (VN89 and A3N89 cells, respectively) was completely inhibited. These data suggest that virus-trans-activated alpha 2-interferon synthesis can be used as a selective inhibitor of HIV replication.
TL;DR: It is shown that the TNF-alpha gene also responds to virus and phorbol 12-myristate 13-acetate in B lymphocytes and that virus is the most potent inducer of TNF
Abstract: Human tumor necrosis factor alpha (TNF-alpha) gene expression can be induced primarily in cells of the monocyte/macrophage lineage by a variety of inducers, including lipopolysaccharide, phorbol esters such as phorbol 12-myristate 13-acetate, and virus or synthetic double-stranded RNA [poly(I).poly(C)]. In this paper we show that the TNF-alpha gene also responds to virus and phorbol 12-myristate 13-acetate in B lymphocytes and that virus is the most potent inducer of TNF-alpha mRNA in both monocyte and B-cell lines. In addition, we show that viral infection coinduces the expression of TNF-alpha and interferon beta mRNA and that viral induction of both genes is blocked by the kinase inhibitor 2-aminopurine. Inhibition of protein synthesis with cycloheximide had no effect on mRNA expression of the genes in one of three cell lines tested (U937) but blocked the viral induction of both genes in another (Namalwa). Thus, the regulatory factors required for mRNA induction of both genes are present prior to the addition of virus in U937 but not in Namalwa cells. However, in a third cell line (JY), cycloheximide blocked viral induction of the interferon beta gene but not the TNF-alpha gene. Taken together, these observations suggest that viral induction of TNF-alpha and interferon beta gene expression may involve overlapping pathways with both common and distinct regulatory factors.
TL;DR: Transcription of class I genes of the major histocompatibility complex (MHC) can be induced by interferons with rapid induction of a DNA‐binding factor, IBP‐1, specific for a site within the interferon response sequence (IRS) of the H‐2Kb promoter.
Abstract: Transcription of class I genes of the major histocompatibility complex (MHC) can be induced by interferons. Treatment of HeLa cells with interferon-gamma induces a DNA-binding factor, IBP-1, specific for a site within the interferon response sequence (IRS) of the H-2Kb promoter. The mol. wt of IBP-1, as estimated by photoactivated protein-DNA crosslinking analysis, is approximately 59 kd. Point-mutation of this binding site abolishes IBP-1 interaction and the ability of the MHC promoter to respond to interferon. Induction of this binding activity is rapid and closely parallels the previously reported time course of transcriptional activation of endogenous MHC class I genes. Treatment of cells with cycloheximide, a protein synthesis inhibitor, blocked the induction of the DNA-binding activity. An oligonucleotide derived from the virus- and double-stranded RNA-inducible promoter of the interferon-beta 1 gene is able to bind IBP-1. Sequences similar to the IBP-1 binding site are found upstream of many interferon-responsive genes.
TL;DR: Observations suggest that interferons may function in regulating human astrocyte HLA-DR expression within the central nervous system.
TL;DR: These studies demonstrate the augmentation of tumor-associated antigens on human carcinoma cells isolated from serous effusions by Hu-IFNs which may be used to enhance the targeting of conjugated MAbs to human carcinomas lesions.
Abstract: Freshly isolated cells from patients with pleural or peritoneal effusions cytologically diagnosed as adenocarcinoma (n = 43), malignant nonepithelial neoplasms (n = 10), and benign (n = 8) were analyzed for expression of constitutive levels of the tumor antigens TAG-72 [recognized by monoclonal antibody (MAb) B72.3] and carcinoembryonic antigen (CEA) (recognized by MAb COL-4) as well as the class I and class II major histocompatibility (MHC) antigens, and the ability of human interferons (Hu-IFNs) to enhance cell surface expression of those antigens as measured by MAb binding. Both type I and type II IFNs enhanced the expression of TAG-72 and CEA and altered the level of expression of the MHC antigens. Comparative studies of three different Hu-IFNs (IFN-alpha A, IFN-beta ser, and IFN-gamma) revealed that IFN-gamma was the most potent in augmenting either B72.3 or COL-4 binding. Unlike the IFN-gamma -mediated induction of the class II human leukocyte antigens, the change in tumor antigen expression consisted of enhanced constitutive antigen expression; de novo induction of either TAG-72 or CEA could not be achieved by either type I or type II IFN. Of 43 effusions isolated from different adenocarcinoma patients, 42 (97.7%) expressed either CEA or TAG-72, and treatment with Hu-IFN increased the level of expression of either antigen in 36 of 42 samples (85.7%). These studies demonstrate the augmentation of tumor-associated antigens on human carcinoma cells isolated from serous effusions by Hu-IFNs which may be used to enhance the targeting of conjugated MAbs to human carcinoma lesions.
TL;DR: This study indicates that the coordinate production of hemopoietic growth factors and interferon, originating from cells that do not classically belong to the immune system, can influence the local and systemic reactions observed during host defence against various infectious agents.
Abstract: Different viruses were compared with the double-stranded RNA poly(rI).poly(rC) and interleukin (IL) 1 for their IL 6-inducing potential in several human and animal cell types. The laboratory viruses Sendai, Mengo and Newcastle disease virus were found to dose dependently stimulate IL 6 production in diploid fibroblasts. A similar effect was obtained with the human pathogens, measles and rubella virus. Concomitantly with IL 6, two other cytokine activities, i.e., interferon-beta and colony-stimulating activity for granulocytes and monocytes, were induced. In addition, these three activities were also produced by fibroblasts in response to Escherichia coli, whereas lipopolysaccharide was only marginally active. The specificity of the induction phenomenon was confirmed by the lack of IL 6 induction with inactivated infectious agents and by the complete neutralization of produced IL 6 by specific antibodies. This study indicates that the coordinate production of hemopoietic growth factors and interferon, originating from cells that do not classically belong to the immune system, can influence the local and systemic reactions observed during host defence against various infectious agents.