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)

Human colorectal carcinoma cells that were treated in vitro with interleukin-6 (IL-6) expressed increased levels of carcinoembryonic antigen (CEA) and normal histocompatibility leukocyte antigen (HLA) class I on their cell surface. The IL-6 mediated increase of CEA expression on the surface of a moderately differentiated colon carcinoma cell line (WiDr) was time- and dose-dependent. A 5-day treatment of the WiDr cells with 100 U IL-6/ml increased the percentage of cells that expressed CEA from 29 to > 80% and enhanced the level of HLA class I expression. The increase in CEA expression as a result of IL-6 treatment was also observed using SDS-PAGE/Western blot analyses, and subsequent Northern blot analyses revealed concomitant increases in CEA-related mRNA transcripts. A comparison of the increases in CEA expression after IL-6, interferon-beta, and interferon-gamma on a nanomolar basis revealed that IL-6 was more potent than either of the interferons. Of 11 different human colorectal tumor cell lines that were treated with IL-6, CEA and/or HLA class I expression were increased in five. Thus, IL-6 can act directly on human colon carcinoma cells and selectively increase the expression of CEA and HLA class I antigens, which may provide some insight into the mechanisms involved in the ability of IL-6 to suppress in vivo tumor growth.
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PMID:Interleukin-6 increases carcinoembryonic antigen and histocompatibility leukocyte antigen expression on the surface of human colorectal carcinoma cells. 147 74

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the proliferation of lymphocytes and on the production of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) was examined in normal human peripheral blood mononuclear cells (PBMC) activated in vitro either by phytohaemagglutinin (PHA) or by the monoclonal antibody to the T-cell receptor OKT3, or by the combination of each of these two stimuli with phorbol myristate acetate (PMA). 1,25(OH)2D3 inhibited the proliferative response of PBMC to PHA; this effect, however, was abrogated by the addition of PMA (1.6 nM), and it was reversed from inhibition to stimulation by higher concentrations of the phorbol ester. In contrast to the PHA-activated cells, 1,25(OH)2D3 had no effect on the proliferative response of PBMC to OKT3. Further, 1,25(OH)2D3 inhibited the release of IL-6 in cultures of PHA-activated PBMC, whereas it stimulated IL-6 with the addition of PMA in these cultures. In contrast to the PHA-activated cells, 1,25(OH)2D3 increased IL-6 release in OKT3-activated cells. IL-1 beta production was not affected in either PHA- or OKT3-activated cells by the presence of the hormone, but it was stimulated by 1,25(OH)2D3 when PMA was used as a co-stimulus with either PHA or OKT3. Finally, 1,25(OH)2D3 inhibited IFN-gamma in both PHA- and OKT3-activated cells, but these effects were attenuated in the presence of PMA. These findings demonstrate that the in vitro effects of 1,25(OH)2D3 on lymphocyte proliferation and cytokine production by PBMC are pleiotropic, and that such pleiotropism depends upon the mode of PBMC activation and presumably the signals that are generated in response to the specific agents used to activate these cells.
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PMID:Signal-dependent pleiotropic regulation of lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3: potent modulation of the hormonal effects by phorbol esters. 149 24

Serum concentrations of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) were determined by commercially available enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) in cancer patients treated with recombinant IL-2 (rIL-2) either as 1-h infusion (3 or 5 x 10(6)/m2) or continuous intravenous infusion for 5 days (3 x 10(6)/m2/day). A significant increase of TNF-alpha and IL-6 serum levels was observed in each patient. One-hour infusion of IL-2 induced a very rapid secretion of TNF-alpha, IL-6 and IFN-gamma with considerably higher peak levels than during IL-2 continuous intravenous infusion. IFN-gamma was released into the blood of all patients receiving IL-2 1-h infusion, but only occasionally during or after IL-2 continuous intravenous infusion. Neither IFN-alpha nor IL-1 were detectable in the serum before, during, or following IL-2 treatment in all patients studied. The kinetics of IL-2 after 1-h infusion fitted to a two-compartment model, suggesting the synthesis of considerable amounts of endogenous IL-2. Following IL-2 1-h infusion, rising TNF-alpha serum levels preceded the increase of serum IFN-gamma or IL-6. The serum peak levels of IFN-gamma and IL-6 decreased rapidly with a half-life of 0.29 to 2.5 h. The concentration time profiles of TNF following 1-h infusion of IL-2 demonstrated a considerably longer half-life than that of intravenously administered recombinant TNF as done in other studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid cytokine release in cancer patients treated with interleukin-2. 150 53

Although 58 patients with peritonitis carcinomatosa underwent multidisciplinary therapy over the last 5 years in our department, about half of them died within 3 months after treatment. In addition, the prognosis was poor for gastric and colon cancer patients, who had macroscopic peritoneal dissemination. Therefore intraoperative intraperitoneal administration of either BRM or anticancer drugs was performed for the microscopic peritoneal dissemination of the cancer, and the immunological response in the peritoneal cavity was examined. In terms of subpopulation of peritoneal exudate cells, neutrophil leucocytes were predominant and thereafter lymphocytes increased. As for the cytokines in the exudate from peritoneal cavity, the concentration of interleukin-6 peaked within 24 hours after administration, followed by a gradual decrease, while the concentration of interferon-gamma was detectable at more than 24 hours after operation, followed by a gradual increase. Tumor necrosis factor-alpha was also detectable in the exudate. Its concentration decreased when both OK-432 and MMC were administered, but it increased when CDDP was administered. The above results indicated that preventive intraoperative intraperitoneal administration of BRM and anticancer drugs should bring about individual immunokinetic modulation in tumor bearing host and both cytokines and immunocytes could play an important role in locoregional tumor immunity.
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PMID:[Clinical studies on locoregional immunochemotherapy of peritonitis carcinomatosa]. 153 Mar 41

Monocyte subpopulations which differ in the expression of Fc receptor for human IgG (FcRI) differentially regulate the T-cell-dependent, pokeweed mitogen (PWM)-induced, polyclonal B-cell response. We, thus, studied the cytokine production in human peripheral blood monocyte and T-lymphocyte cultures activated with this lectin. Monocytes or their FcR+ and FcR- subpopulations stimulated with PWM were cultured with or without T lymphocytes or their CD4+ and CD8+ subsets. Both monocyte subpopulations cultured alone produced similar amounts of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), but FcR- monocytes showed significantly enhanced ability to secrete interleukin-1 (IL-1). T cells, especially CD4+, added to monocyte cultures enhanced IL-1 production. This enhancement was presumably due to interferon-gamma (IFN-gamma) release by T lymphocytes, since this lymphokine enhanced IL-1 secretion when added to PWM-stimulated cultures of monocytes. Addition of monocytes, in particular the FcR+ subpopulation, greatly enhanced production of IFN-gamma by T lymphocytes. Although both T-cell subsets produced IFN-gamma, the CD4+ cells were more efficient. These results indicate that in PWM-stimulated cultures subpopulations of monocytes differ in secretion of cytokines, which might explain their differential effect on T-cell-dependent immune responses in vitro.
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PMID:FcR+ and FcR- monocytes differentially secrete monokines during pokeweed mitogen-induced T-cell-monocyte interactions. 153 81

Cytokine mRNA production in the thyroid tissues of patients with various thyroid diseases was analysed by in situ hybridization. In addition, infiltrating leukocytes were characterized by immunohistologic studies using the alkaline phosphatase anti-alkaline phosphatase (APAAP) staining technique. The following clinical material was investigated: two cases of Graves' disease, one with high and the other with a low amount of infiltrating leukocytes as well as two cases of non-toxic goitre also showing considerable quantities of infiltrating cells. The hybridization was performed on tissue sections with antisense probes for interferon-gamma (IFN-gamma), IFN-alpha E, IFN-beta, interleukin-6 (IL-6) and IL-1 beta. A small number of individual cells were found to express high levels of mRNA for IFN-gamma, IL-1 beta and measurable amounts of IL-6 throughout the tissue sections. However, IFN-alpha E or IFN-beta were not detected. Cytokine expressing cells were noted in the tissue of one patient with Graves' disease and in two cases with non-toxic goitre. In these samples a high amount of infiltrating leukocytes (CD45+) was detected, especially CD3+, CD8+, CD4+ and CD45RA+ T cells, in addition to B cells and macrophages. In one case an unusually large amount of T cell receptor gamma/delta+ (TcR gamma/delta+) cells was found. However, one sample of thyroid tissue derived from a patient with Graves' disease was poorly infiltrated and showed few cells expressing cytokines. In conclusion, using thyroid tissue as an example, our data suggest that the application of in situ hybridization with antisense RNA permits the study of cytokine production in tissues of both autoimmune and non-autoimmune origin.
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PMID:In situ hybridization of the mRNA for interferon-gamma, interferon-alpha E, interferon-beta, interleukin-1 beta and interleukin-6 and characterization of infiltrating cells in thyroid tissues. 153 76

We have established previously that human thyroid epithelial cells (TEC) from patients with autoimmune thyroiditis are able to synthesize cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6). This paper examines TEC in sections from autoimmune thyroiditis for the in vivo production of tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) using the combined techniques of in situ hybridization and immunohistochemistry. Thyroid tissue from patients with Graves' disease, Hashimoto's disease and non-toxic goitre was examined and both mRNA and the protein of TNF-alpha were detected in TEC on frozen sections. Representative figures of only Graves' samples are illustrated in this paper. In contrast, using the same methods, IFN-gamma was detected only in the infiltrating cells and not in TEC of thyroid tissue from the patients.
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PMID:Detection of in vivo production of tumour necrosis factor-alpha by human thyroid epithelial cells. 157 93

Recently, the mitogenic effects of the Mycoplasma arthritidis supernatant, MAS, and the induction of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) by MAS have been described. In the present series of experiments we investigated human peripheral blood mononuclear cells (PBM) and human spleen cells with respect to their production of these and other cytokines. In human spleen cell cultures and PBM, MAS induced the synthesis of interleukin-1 alpha (IL-1 alpha) and IL-1 beta. Both interleukins were secreted faster and in higher amounts by PBM. IL-6 was also induced by MAS in PBM and human spleen cells. The amounts of IL-6 measured by ELISA were higher in PBM, whereas the biological activity of IL-6 was higher in spleen cell cultures. T-cell products such as IL-2, IL-4, and IFN-gamma were also induced by MAS in PBM and spleen cells. The kinetics of IFN-gamma and IL-4 induction were negatively correlated. In PBM we found low levels of IL-4 and high IFN-gamma induction, whereas in spleen cells high titers of IL-4 and low IFN-gamma titers were observed. Collectively, our results indicate that MAS induces different networks of cytokine interactions depending on the organ from which the cells are derived.
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PMID:Induction of cytokines in human peripheral blood and spleen cells by the Mycoplasma arthritidis-derived superantigen. 158 16

Although interferon-gamma has been shown to effectively prime macrophages for enhanced production of tumor necrosis factor-alpha (TNF alpha), it is reasonable to assume that other cytokines present in the extracellular environment may likewise facilitate cytokine biosynthesis. For example, interleukin-6 (IL-6) is synthesized by synovial lining macrophages and fibroblasts, and has been detected (along with TNF alpha) in rheumatoid synovial effusions. Therefore, the purpose of the present study was to determine whether IL-6 influences the production of IL-1 beta and/or TNF alpha by THP-1 macrophages. Although IL-6 treatment alone resulted in only a slight increase in TNF alpha levels, administration of IL-6 followed by Sal. minnesota LPS resulted in a synergistic potentiation of TNF alpha production by THP-1 macrophages. The priming effect of IL-6 could be reversed by boiling, or by the addition of a neutralizing polyclonal antibody against IL-6. Notably, IL-6 only weakly enhanced interleukin-1 beta production. In summary, the ability of IL-6 to potentiate TNF alpha production by THP-1 macrophages may provide insight into the regulation of the cytokine network in inflammatory diseases, such as rheumatoid arthritis.
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PMID:Interleukin-6 can prime THP-1 macrophages for enhanced production of tumor necrosis factor-alpha in response to LPS. 160 43

The capacity of synoviocytes to participate in inflammatory responses may be altered by the cytokine-enhanced expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). To examine this possibility, the ability of selected cytokines to enhance ICAM-1 expression was examined. The data indicated that each of these cytokines (interleukin-1 beta greater than tumor necrosis factor-alpha, interferon-gamma much greater than interleukin-6) can up-regulate synoviocyte ICAM-1 expression. This can potentially increase the ability of these cells to interact with infiltrating inflammatory cells, thereby propagating immunologically mediated inflammation such as occurs in rheumatoid synovitis.
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PMID:Regulation of the expression of adhesion molecules by human synoviocytes. 160 27


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