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)

B-cell stimulatory factor 2 (BSF-2) is a lymphokine which induces the final maturation of B cells. BSF-2 acts on a variety of cells other than B cells, and moreover, expression of BSF-2 mRNA is detected in interleukin-1 beta-stimulated glioblastoma and astrocytoma cell lines. Here, we studied the function of BSF-2 on pheochromocytoma PC12 cells, a model system for induction of neuronal differentiation. PC12 cells possess specific receptors for BSF-2. The BSF-2-stimulated PC12 cells expressed the c-fos proto-oncogene transiently, and they began to change morphologically to neurite-extending cells after several days. The number of voltage-dependent Na+ channels was also increased.
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PMID:Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6. 326 80

We describe an interleukin, termed interleukin 5, that is the recombinant product previously referred to as T-cell-replacing factor (TRF), B-cell growth factor II (BCGF II), or killer-helper factor (KHF). TRF has been defined as a T-cell-derived lymphokine that acts on activated B cells as a B-cell differentiation factor. We have previously demonstrated that TRF is identical to BCGF II and induces expression of receptors for interleukin 2 (IL-2) on activated B cells. We also have reported that KHF can induce not only expression of IL-2 receptors on peanut agglutinin-binding (PNA+) thymocytes but also generation of cytotoxic T lymphocytes (CTL) in PNA+ thymocytes in the presence of IL-2. We show here that culture supernatants of T-cell hybridomas that produce TRF as well as TRF purified by high-pressure liquid chromatography (HPLC-TRF) have KHF activity and generate CTL in PNA+ thymocytes in the presence of stimulator cells and IL-2. Moreover, translation products (recombinant TRF) of Xenopus oocytes injected with cDNA encoding for murine TRF (BCGF II) also exert KHF activity. A rat monoclonal anti-TRF antibody TB13 can block generation of CTL by HPLC-TRF or recombinant TRF. These results indicate that TRF acts not only on B cells as BCGF II but also on PNA+ thymocytes as KHF. In view of the diverse activities and targets of TRF, we propose that TRF refers to a different interleukin, interleukin 5.
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PMID:Interleukin 5, a T-cell-derived B-cell differentiation factor also induces cytotoxic T lymphocytes. 349 3

The proliferation and maturation of antigen-stimulated B cells are regulated by several soluble factors derived from macrophages and T cells. These soluble factors have been functionally divided into two groups; B-cell growth factor (BCGF) and B-cell differentiation factor (BCDF). However, this distinct classification and identification of B-cell factors should be reexamined after the recent cloning of cDNA encoding IgG1 induction factor (IL-4) from a 2.19 T-cell line. This factor induces not only an elevated IgG1 response in B cells activated by lipopolysaccharides but also hyper-Ia expression in B cells. IL-4 is identical to B-cell stimulating factor-1 (BSF-1) which induces DNA synthesis when given together with anti-IgM antibodies. Furthermore, this lymphokine has growth factor activities for both T and mast cells. Another well characterized B-cell factor is T-cell replacing factor (TRF). Although TRF was previously classified as a BCDF, a partially purified preparation of TRF was suggested to have BCGF II activity. The identity of TRF with BCGF II was proved by its cDNA cloning and the name IL-5 was proposed for this lymphokine.
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PMID:[Molecular cloning of cDNAs encoding B-cell growth factors]. 349 51

Purified peripheral murine T cells, in the presence of concanavalin A, can be activated to produce interleukin 2 (IL-2) through stimulation either with a previously described murine lymphokine designated T cell-activating factor (TAF) or with a cloned human lymphokine that has been called beta 2 interferon, B-cell-stimulatory factor 2, hybridoma growth factor, inducible 26-kDa protein, or hematopoietic colony-stimulating factor 309 by different investigators. We and others propose the designation interleukin 6 (IL-6) for the latter molecule. Our experiments demonstrate that either murine TAF or human IL-6 can restore the ability of purified T cells to proliferate in response to Con A or antibodies against the T-cell antigen receptor. Most if not all of the proliferation can be blocked by antibodies against the alpha chain of the IL-2 receptor. Furthermore, highly purified CD8- T cells can be activated by IL-6 in the presence of Con A to secrete IL-2. We propose that IL-6 and murine TAF are important "second signals" in primary antigen-receptor-dependent T-cell activation. Whether or not murine TAF is a homologue of human IL-6 remains to be determined.
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PMID:B-cell-stimulatory factor 2 (beta 2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells. 349 11

Transfer of cytokine genes into tumor cells has proven a valuable approach for cancer treatment. In order to generate a more effective cancer vaccine, we transfected the human interleukin-6 (IL-6) gene into B16 melanoma cells. A B16 cell clone secreting the highest level of IL-6 was obtained by G418-resistant selection, limiting dilution and IL-6 assay. The IL-6-gene-transfected tumor cells exhibited in vitro growth inhibition, reduced tumorigenicity and decreased metastatic competence. After immunization with the inactivated IL-6-gene-transfected vaccine, the murine cytotoxic T lymphocyte activity, natural killer activity and lymphokine-activated killer activity increased markedly. After treatment with the vaccine, the tumor-bearing mice showed significant growth inhibition of subcutaneous tumor, reduction in pulmonary metastases and extension of survival time. The above therapeutic effect was better when low-dose IL-2 was administered simultaneously, although this dosage of IL-2 had no in vivo antitumor effect. These data demonstrated that IL-6-gene-transfected cancer vaccine has a potent antitumor effect via efficient induction of antitumor immunity, and a better therapeutic effect could be achieved when the vaccine is combined with low-dose IL-2 as adjuvant.
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PMID:Induction of antitumor immunity and treatment of preestablished tumor by interleukin-6-gene-transfected melanoma cells combined with low-dose interleukin-2. 749 43

A possible correlation between the pathogenicity of autoimmune T cells and their lymphokine production, expression of functional adhesion molecules and expression of some surface antigens was examined. We used four retinal antigen-specific Lewis rat T cell lines and sublines: one specific to the major pathogenic epitope of the human retinal soluble antigen (S-Ag; residues 337-356), and three specific to the major pathogenic epitope of the bovine interphotoreceptor retinoid binding protein (IRBP; residues 1177-1191). The lines have different degrees of uveitogenicity, from highly pathogenic to nonpathogenic. All four T cell lines produced roughly equivalent amounts of interferon-gamma, lymphotoxin/tumor necrosis factor (TNF alpha/beta), interleukin-3, interleukin-6 and transforming growth factor-beta. Interleukin-4 activity could not be detected. The lines also expressed similar levels of functional adhesion molecules, as measured by binding to cultured rat aorta endothelial cells. The nonpathogenic subline, however, was the lowest responder to antigenic stimulation with respect to proliferation and interleukin-2 production. Examination of cell surface antigens showed that in contrast to the other lines, the majority of cells in the nonpathogenic subline lacked detectable expression of CD4. No difference was found in the level of expression of the IL-2 receptor and T cell antigen receptor among the four lines. Because CD4 is the restricting element in these lines, reduced CD4 expression in the nonpathogenic subline may at least partially explain its poor response in vitro to antigenic stimulation. All three attributes could be connected to lack of pathogenicity of this line in vivo. These results support the contention that class II-restricted recognition of autoantigen within the neuroretina by uveitogenic T lymphocytes must occur as an initial step in the pathogenesis of EAU. A defect in this step will preclude pathogenesis regardless of some other functional attributes possessed by effector T cells, such as production of inflammatory lymphokines and expression of adhesion molecules.
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PMID:Uveitogenic T lymphocytes in the rat: pathogenicity vs. lymphokine production, adhesion molecules and surface antigen expression. 752 41

Lymphokines play an important role in immune responses to viruses by modulating functions of T lymphocytes. In the present study, we examined the effects of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-7 (IL-7), and interferon gamma (IFN gamma) on proliferation, cytotoxic activity and lymphokine production of a dengue virus-specific CD8+ human cytotoxic T lymphocyte (CTL) clone. IL-2 and IL-7 induced proliferation of the CD8+ CTL clone in the presence or absence of specific antigen, while IFN gamma suppressed proliferation of the clone. IL-7 and IFN gamma augmented dengue virus-specific cytotoxic activity without inducing non-specific cytotoxic activity, and IL-2 induced non-specific cytotoxic activity. IL-2 induced IFN gamma production by the CD8+ CTL clone. IL-4 and IL-6 did not modulate the functions of the CD8+ CTL clone in these experimental conditions. These results suggest that functions of dengue virus-specific CD8+ CTL are modulated by IL-2, IL-7 and IFN gamma, and that IL-7 is a lymphokine useful to induce growth and to maintain specific cytotoxic activity of CD8+ CTL clones in vitro.
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PMID:Modulation of the functions of dengue virus-specific human CD8+ cytotoxic T cell clone by IL-2, IL-7 and IFN gamma. 762 98

Leucocyte functions and the influence of chemoradiotherapy were examined in three age groups of patients with oral cancer. The groups consisted of 66 patients below 65 years old (group A): 40 patients between 65 and 80 years old (group B); 20 patients over 80 years old (group C). 20 healthy individuals (45.8 +/- 9.6 years old) were chosen as controls. Originally, no significant differences in leucocyte count, CD3 population, CD4/CD8 ratio, natural killer activity or phagocytosis of polymorphonuclear leucocytes (PMNL) were found in the patients. However, T cell blastogenesis, lymphokine-activated killer cell activity and superoxide production of PMNL were all suppressed. These functions were further suppressed by cancer therapy, the greatest suppression being seen in group C. Compared to controls and group A, the generation of interleukin-1, interleukin-6, tumour necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor were markedly suppressed in group C. These results show that very old cancer patients are already in an immunologically suppressed condition and that the leucocyte functions of these patients are further impaired by cancer therapy.
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PMID:Influence of aging and chemoradiotherapy on leucocyte function in oral cancer patients. 763 87

Aggregation studies have become a useful criterion for analyzing leukocyte motility and activation in vitro. The T-cell-derived lymphokine human leukocyte inhibitory factor (LIF) is a modulator of many important polymorphonuclear (PMN) functions in addition to aggregation such as chemotaxis, lysosomal degranulation, phagocytosis, bactericidal killing, augmented antibody-dependent cellular cytotoxicity (ADCC), induction of neutrophil Fc-gamma, complement type-1 and FMLP receptors, and production of superoxide and H2O2. Our investigations focused on the ability of LIF to modulate the aggregation of macrophages (MO) induced by calcium ionophore A23187. The ionophore A23187 directly induced potent aggregation of macrophages, which was markedly enhanced when the cells were pretreated with LIF. However, the addition of LIF in the absence of other costimuli did not directly induce MO aggregation. LIF was shown to enhance PMN aggregation induced by N-formyl-Met-Leu-Phe (FMLP), but did not augment the aggregation of FMLP-stimulated macrophages, indicating a cellular specificity of aggregation-inducing costimuli following LIF priming. Additional cytokines examined for possibly inducing MO aggregation were interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF), and interleukin-6 (IL-6); all proved to be incapable of inducing aggregation directly, nor did they enhance the effect of A23187 ionophore on macrophage aggregation. Additionally, we found that LIF can directly stimulate MO to activate specific pathways of the arachidonic acid cascade, inducing the synthesis and release of thromboxanes and leukotriene B4. LIF did not augment the potent ability of A23187 to induce increased production of LTB4 or TxA2 by human MO. These new results coupled with our previously published data indicate that LIF can enhance the activation of both MO and PMN leukocytes when exposed to either A23187 or FMLP, respectively. Moreover, these data suggest that LIF can contribute directly to monocyte-macrophage leukocyte activation, in addition to PMN activation, during inflammatory responses, resulting in greater cell aggregation, activation, and specific proinflammatory arachidonic acid product release.
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PMID:Leukocyte inhibitory factor (LIF) potentiates human macrophage aggregation and activation responses to calcium ionophore A23187 and directly induces leukotriene B4 and thromboxane A2 release. 829 72

Interleukin-6 (IL-6) is a cytokine that acts on a variety of cell types, including myeloid progenitor cells and B and T lymphocytes. It has been found to activate cytotoxic T cells and natural killer (NK) cells and to induce T-cell-mediated antitumour effects in animal models. In a phase I clinical trial of recombinant human IL-6, 20 patients with advanced cancer were entered to receive daily subcutaneous injections of IL-6 over 7 days followed by a 2-week observation period and another 4 weeks of daily IL-6 injections. Doses varied between 0.5 microgram/kg and 20 micrograms/kg body weight and immune functions were monitored throughout. At all dose levels IL-6 administration led to a marked increase in serum levels of C-reactive protein and a moderate rise in complement factor C3. The proportions of CD4, CD8 or HLA-DR lymphocytes in peripheral blood did not alter with IL-6 treatment nor did the in vitro proliferation of peripheral blood mononuclear cells induced by either phytohaemagglutinin, pokeweed mitogen or fixed Staphylococcus aureus. By contrast, NK cell activity, lymphokine-activated killer (LAK) cell activity and proliferation induced by in vitro culture with interleukin-2 (IL-2) were suppressed at doses exceeding 2.5 micrograms/kg. Serum IgE levels were consistently elevated over the IL-6 dose range but IgM, IgG and IgA levels were unaffected. In summary there is a dose-dependent induction of acute-phase proteins by in vivo IL-6 treatment. At higher IL-6 doses there is a suppressive effect on NK and LAK activity measured in vitro. IL-6 may thus be useful in combination cytokine therapies that seek to suppress LAK and favour cytotoxic T lymphocyte responses. The rise in IgE levels in response to IL-6 was unexpected and suggests a more pivotal role than previously known for the control of IgE production; this could include IgE-related diseases.
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PMID:Immune function of patients receiving recombinant human interleukin-6 (IL-6) in a phase I clinical study: induction of C-reactive protein and IgE and inhibition of natural killer and lymphokine-activated killer cell activity. 830 67


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