Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is difficult to induce anti-tumor immunity in tumors with low antigenicity. In order to develop a more effective method of immunotherapy, we transfected interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6) genes into Lewis lung carcinoma (LLC) cells. Then, 1 x 10(6) LLC-IL-2, LLC-IL-4 or LLC-IL-6 cells were transplanted into C57BL/6 mice subcutaneously. All mice transplanted with LLC-IL2 and half those with LLC-IL-4 rejected the tumor cells. Survival time of LLC-IL-6 transplanted mice was significantly shorter than that of LLC transplanted mice, with no difference in tumor growth. These data suggest that transplantation of IL-2 or IL-4 gene transfected cells could effectively induce immunity against LLC. IL-6 transfection did not induce immunity, but induced cachexia.
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PMID:[Induction of tumor immunity by cytokine cDNA transfected Lewis lung carcinoma]. 130 38

In previous reports, we demonstrated that adoptively transferred T cells homed to the tumor site (among other sites) and that amplification of immune responses occurred in situ leading to the generation of cytotoxic CD8+ tumor-infiltrating lymphocytes (TIL) and macrophages. The present report extends these findings and shows that following adoptive immunotherapy (AIT) of mice bearing the immunogenic transplanted methylcholanthrene-induced rhabdomyosarcoma (MCA/76-9) there was a differential expansion of CD4+ and CD8+ TIL, the numbers peaking on days 6 and 8, respectively. At this time, CD8+ TIL accounted for the majority of Thy-1+ cells. Northern analyses of RNA extracted from positively selected (by panning) Thy-1+, CD8+ and CD4+ TIL isolated 8 days after AIT indicated the following: in five separate experiments, CD4+ cells expressed three- to sixfold more interleukin (IL)2 mRNA and six- to eightfold more IL6 mRNA than CD8+ cells, while CD8+ TIL expressed three- to sixfold more IL2 receptor (IL2R) mRNA and four- to sixfold more interferon-gamma mRNA than CD4+ cells. TIL cultured in 10% fetal bovine serum failed to release IL2 over a 24-h period, whereas both IL6 and interferon-gamma activities were demonstrable. The level of IL2R mRNA expression was reflected by a vigorous proliferative response of CD8+ TIL to exogenous recombinant IL2 and only a low response by CD4+ cells suggesting that most of the CD4+ TIL were in the resting stage. This was confirmed when it was shown that the incubation of panned CD4+ TIL with IL2 supplemented with irradiated spleen cells and "spent" 76-9 tumor culture supernatant (as a source of antigen) induced expansion of TIL resulting in a population consisting of greater than 90% CD4+ TIL. The overall data suggest that the relatively deactivated state of the CD4+ TIL at this particular time reflects the status of the rejection process in terms of the absence or low concentration of stimulating tumor-associated antigen.
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PMID:Differential in situ expansion and gene expression of CD4+ and CD8+ tumor-infiltrating lymphocytes following adoptive immunotherapy in a murine tumor model system. 190 16

Maturation of cytolytic T lymphocytes from nonlytic precursors requires cytokines in addition to IL2. Interleukin-6 is the principal cytokine that cooperates with IL2 in the induction of CTL differentiation from murine and human thymocyte precursors. However, a cytotoxic differentiation factor (CDF) role of IL6 for mature T cells is challenged by data indicating that IL2 alone is sufficient for CTL generation. The aim of this study was to identify a model system in which IL6 acted as a CDF for human peripheral T cells. We noted that IL6 was endogenously produced by CTL clones in the course of their expansion with APC, lectin, and IL2. The majority of several hundred T-cell clones, both CD4+ and CD8+, produced IL6 in response to relatively high doses of IL2. Other experiments that compared the cytolytic function of CTL clones cultured in the presence of IL6 with that of the same clones cultured in the absence of IL6 demonstrated that IL6 contributes to the cytolytic ability of the majority of human CTL clones. Our data suggest that IL6 acts in an autocrine fashion to support CTL differentiation in human T-cell clones.
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PMID:Interleukin-6 is constitutively produced by human CTL clones and is required to maintain their cytolytic function. 191 33

Most B-cell differentiation systems are complicated by the fact that they are both T-cell- and monocyte-dependent. Immobilized anti-CD3 antibodies induce monocyte-independent T-cell activation, allowing investigation of the role of interleukin-6 (IL6) in the process of B-cell differentiation. We observed that in this system, the addition of monocytes to purified lymphocytes does not influence T-cell proliferation but it does enhance the induction of Ig production. IL6 can specifically replace monocytes in this enhancing effect on both IgM and IgG production. Anti-CD3-induced Ig production appears to be dependent on both IL2 and IL6 since it was inhibited by anti-CD25 (anti-IL2-R) antibodies as well as by anti-IL6 antibodies. Kinetic studies of IL6 addition showed that IL6 is only necessary during the first two days of culture. Our data indicate that IL6 plays an essential role in anti-CD3-induced Ig production, but not as a terminal differentiation factor.
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PMID:Interleukin-6 enhances human Ig production, but not as a terminal differentiation factor for B lymphocytes. 214 20

The molecular mechanism of the interleukin (IL) 2-induced differentiation of human B cells has been investigated. The experimental results show that Staphylococcus aureus Cowan strain I (SAC) activation alone induces IL6 secretion from B cells. When B cells were activated by SAC, there was an increased transcription of the IL6 mRNA. It reached the peak level by 6 h and rapidly decreased to an undetectable level within 24 h. The IL6 concentration in the culture supernatants reached the peak at 24-48 h and decreased slightly in the following culture periods. Since IL 2 alone could induce IgG secretion, whether exogenous IL6 was added or not, and IL2 did not increase autocrine IL6 synthesis, it appears that IL2 induces the IL6 responsiveness of SAC-activated B cells to differentiate in the later stage of the culture. The addition of polyclonal anti-IL6 antibody inhibited IgG secretion. The antibody still efficiently blocked IgG secretion up to day 5, indicating an important role of autocrine IL6 in the IL2-driven B cell differentiation. However, the saturation dose of anti-IL6 antibody inhibited 50%-70% of IgG secretion, suggesting that IL2-induced B cell differentiation appears to be mediated by other factors besides IL6.
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PMID:Recombinant interleukin (IL) 2-induced human B cell differentiation is mediated by autocrine IL6. 260 40

We investigated the regulation of IL6 biological activity, de novo synthesis, and mRNA levels in adult vascular endothelial cells (EC) by bacterial endotoxin or inflammatory cytokines. Cells incubated without stimulus released scant IL6 activity. IFN gamma, IL2, or PDGF did not augment IL6 release from EC. LPS, lipid A, and TNF increased IL6 release modestly (5 to 20-fold), while recombinant IL1s (rIL1s) stimulated this process 100 to 400-fold. Differential release of IL6 from EC treated with LPS or rIL1 continued for at least 144 hr. Exposure to LPS or rIL1 caused EC to synthesize IL6 de novo. EC secreted the newly synthesized IL6 into the supernatant, rather than retaining it within or bound to cells. EC accumulated IL6 mRNA after 3 hr of exposure to rIL1. However, we could only detect IL6 message in cells incubated with LPS under "superinduction" conditions with cycloheximide, consistent with lower levels of IL6 biological activity in response to LPS compared to IL1 stimulation. We propose that local production of IL6 by vascular EC, which comprise the barrier between tissues and the blood, may influence regional immune and inflammatory responses.
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PMID:Adult human vascular endothelial cells express the IL6 gene differentially in response to LPS or IL1. 278 20

The ability to detect feline cytokine expression would allow further characterization of the feline immune system. Bioassays are currently available for the measurement of feline IL2, IL6 and TNF alpha but not for other biologically important cytokines. To detect the expression of other cytokines, a reverse transcription-polymerase chain reaction (RT-PCR) procedure was developed. Since feline cytokine gene sequences other than TNF alpha were not available, mammalian DNA and mRNA sequences for IL2, IFN gamma, IL4, IL6, IL10, IL12 and beta-actin, obtained from the Genbank database were compared and oligonucleotide primers chosen from consensus sequences. To validate the cytokine and beta-actin primers, peripheral blood mononuclear cells from specific pathogen free (SPF) cats were cultured in the presence of Con A for various periods of time (0-72 h). RNA was collected, reverse transcribed into cDNA, and the cDNA was amplified by PCR with each set of cytokine primer pairs. RT-PCR products were hybridized with specific 32P end-labeled internal oligonucleotide probes and then analyzed with the AMBIS imaging system to determine the kinetics of cytokine mRNA production. The beta-actin signal was used to control for sample to sample variation in the quantity of mRNA and variation in the RT and PCR reactions. Peak mRNA expression for most cytokines was found to occur between 2 to 4 h of Con A stimulation. mRNA expression was correlated with cytokine bioactivity for IL2 and IL6. Peak IL2 bioactivity occurred after 8 h of Con A stimulation, 4 h after the mRNA expression had peaked. Although IL6 mRNA expression peaked between 2 and 4 h of stimulation, bioactivity was not detected until 8 h of stimulation and continued to increase over the next 24-48 h.
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PMID:A reverse transcription-polymerase chain reaction technique to detect feline cytokine genes. 760 28

This study was carried out to test the hypothesis that, in chronic hepatitis (CH), inflammatory processes, including viral replication, host immune response, and hepatocyte destruction, are regulated by a cytokine network in the liver. Expression of the mRNA of the cytokines IL1-beta, IL2, IL4, IL5, IL6, TNF-alpha, and IFN-gamma, the lymphocyte markers CD4 and CD8, and the HLA class I molecule, beta 2-microglobulin (B2MG) in the liver tissue of 20 CH(C) cases and 9 CH(B) patients was investigated by the reverse transcription polymerase chain reaction (RT-PCR) method. TNF-alpha, CD4, and B2MG mRNA were detected in 100% of cases of in both CH(B) and CH(C). The expression rates of IL1-beta, IL2, IL4, IFN-gamma, and CD8 mRNA were 80%, 40%, 25%, 40%, and 80% in CH(C) and 88.9%, 44.5%, 30%, 55.6%, and 100% in CH(B). IL6 mRNA was detected only in CH(B), in 22.2% of cases, IL5 mRNA was not detected in either CH(B) or CH(C). IL2, IL4, and IFN-gamma mRNA were expressed significantly more frequently in patients who had high serum ALT and a high histological activity index (HAI) score. There was no difference in cytokine expression between CH(B) and CH(C), except in IL6, suggesting the existence of a common immunopathogenesis for CH(B) and CH(C). In chronic viral hepatitis, IL1-beta and TNF-alpha appear to play a major role in immune responses and IL2, IL4, and IFN-gamma seem to be associated with increased cytotoxic T cell response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression rate of cytokine mRNA in the liver of chronic hepatitis C: comparison with chronic hepatitis B. 771 13

Oncostatin M (OSM) is a member of the interleukin-6 (IL6)-related cytokine subfamily that includes IL6, IL11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor and cardiotrophin-1. While human OSM has been characterized and the bovine OSM gene was recently cloned, the murine counterpart had not been identified. Here we describe molecular cloning of murine OSM as an immediate early gene induced by a subset of cytokines including IL2, IL3 and erythropoietin (EPO) in myeloid and lymphoid cell lines. The induction kinetics of OSM are rapid and transient, reaching a maximal level within 30-60 min and decreasing thereafter. Induction of OSM depends on the signals generated by the membrane-proximal region of the EPO receptor as well as that of the beta chain of the IL3/GM-CSF receptor, which activate JAK2 and STAT5. About 100 bases upstream of the transcription initiation site of the OSM gene contains a possible STAT5 binding site which is essential for IL2, IL3 and EPO-dependent promoter activity of the OSM gene. Expression of STAT5 and the EPO receptor in COS cells conferred EPO-dependent activation of the OSM promoter. Moreover, the mutant IL2 receptor lacking the ability to activate STAT5 induced c-myc but failed to induce OSM. Thus OSM is one of the common targets of a subset of cytokines that activate STAT5. The murine OSM gene is located near to the LIF gene, expressed at high levels in bone marrow and possesses similar biological activity to human OSM. Identification of murine OSM as a cytokine-inducible immediate early gene provides a new insight into the physiological function of this unique cytokine.
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PMID:Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. 860 75

Serum levels of interleukin-6 (IL-6) are elevated in acute and chronic hepatitis B patients. The effect of IL-6 and its transcription factor of NF-IL6 (a nuclear factor for IL-6) on hepatitis B virus (HBV) enhancer 1 (Enh1), which controls HBV X expression, were investigated in HepG2 cells. Twenty ng/ml of IL-6 increased 4-fold the enhancer activity of Enh1 according to the CAT assay. The IL-6 stimulation was abolished by introducing a mutation either in an AP-1-related site or a C-stretch sequence in the Enh1 sequence, demonstrating that the cis-elements are necessary for the IL-6 response. Co-transfection of NF-IL6 expression plasmid similarly increased the enhancer activity of Enh1 through both binding sites. Further, a specific complex formation of the Enh1 was detected using HepG2 nuclear lysates by electromobility shift assays, and the complex formation was increased in the lysates of cells treated with IL-6 and NF-IL6-transfection. In competition assays, one half of the complex formed was found to remain in the presence of 500-times excess competitor DNA fragment harboring NF-IL2 binding site, suggesting indirect binding of NF-IL6 to the Enh1 sequence. These results indicate that IL-6 increased the enhancer activity of HBV Enh1 through signal transduction pathways, indirectly involving NF-IL6, and may control HBV X expression and viral replication in HBV infected liver.
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PMID:Human hepatitis B virus enhancer 1 is responsive to human interleukin-6. 926 Jun 90


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