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)

The authors evaluate the involvement of various cytokines (interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor alpha and gamma-interferon) in the pathogenesis of multiple sclerosis. The cytokines might participate in nervous tissue damage by promoting demyelination and oligodendrocyte injury or by enhancing local immune response. In addition, several authors reported increased levels of some cytokines in serum and cerebrospinal fluid of patients with multiple sclerosis. These findings suggest that cytokines can play a significant role in the immunopathogenesis of the disease.
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PMID:Cytokines in the pathogenesis of multiple sclerosis. 129 76

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

Epstein-Barr virus (EBV)-induced in vitro infection of peripheral blood mononuclear cells (PBMCs) leads to a polyclonal proliferation and immortalisation of B lymphocytes. In the present study we determined the effects of three different cytokines, interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6), and the tumour promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on EBV-immortalised B lymphocytes. These factors have known activities on normal B cells. IL-4 and IL-6 increased significantly EBV-B cell proliferation after 3 and 5 days of culture, where IL-2 had no effect. The effect of IL-4 and IL-6 on EBV-B cells was abolished after pre-incubation with anti-IL-4 and anti-IL-6 neutralising antisera, respectively. TPA induced a dose dependent inhibition of proliferation both in serum free and 10% fetal calf serum (FCS) supplemented culture medium. Combinations of TPA and interleukins did not restore lymphoblastoid cell proliferation to background levels. All possible combinations of the three cytokines showed no synergistic or antagonistic effect on proliferation. TPA induced significant phenotypic changes of EBV immortalised B lymphocytes, by increasing IL-2 receptor (IL-2R) expression and decreasing CD20 and CD23 antigen expression. Other B cell differentiation antigens; HLA-DR, CD19, and transferrin receptor (CD71), did not demonstrate significant changes. A dose dependent inhibition of CD21 and increase in CD22 expression was observed in 2 out of 3 lymphoblastoid cell lines tested.
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PMID:Effects of phorbol esters and cytokines (interleukin-2,-4, and -6) on the proliferation and surface phenotype of Epstein-Barr virus immortalised human B lymphocytes. 133 96

The kinetic profile of cytokine gene expression in normal human peripheral mononuclear cells (MNC) activated by an anti-CD3 monoclonal antibody was studied. The presence or absence of 10 different cytokine mRNA were measured in a polymerase chain reaction (PCR) assisted mRNA amplification assay. After 2 h of stimulation the mRNA for interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were detectable and remained present during the whole time period studied (22 h). Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were detected after 4 h, while interleukin-10 (IL-10) mRNA did not appear until after 7 h; they all remained expressed at 22 h. A transient expression of interleukin-4 (IL-4) mRNA was observed between 4 and 7 h of stimulation. No gene expression of granulocyte colony stimulating factor (G-CSF) was detected at any time. These results show that anti-CD3 stimulation of MNC leads to a rapid sequential induction of different cytokine mRNA, some with a very transient expression.
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PMID:OKT3-induced cytokine mRNA expression in human peripheral blood mononuclear cells measured by polymerase chain reaction. 143 86

Recent investigations of immunologic events in systemic sclerosis focus on the identification of which immune system cells are participating in the disease process, what antigens are stimulating the T and B cells, which cytokines are involved, and which cell adhesion molecules promote cell-cell and cell-extracellular matrix interactions. Increased numbers of gamma/delta and activated CD4+ T cells are present in involved skin of line-200 chickens, an animal model of systemic sclerosis. CD4+ T cells from patients with systemic sclerosis are stimulated by human type I collagen, and immunoglobulins from some patients with systemic sclerosis bind retroviral proteins, the terminal galactosyl (alpha 1-3)-galactose disaccharide of laminin, or a 138 amino acid region of the PM-Scl antigen. The development of an anticentromere antibody response in patients with systemic sclerosis appears to require the presence of a polar amino acid at position 26 in the antigen-binding cleft of the HLA-DQB1 molecule. Interleukin-2, interleukin-4, interleukin-6, and transforming growth factor-beta have been implicated as cytokines that may be involved in the pathogenesis of systemic sclerosis. Increased expression of intercellular adhesion molecule 1 (ICAM-1) on systemic sclerosis fibroblasts is responsible for increased binding of T cells to those fibroblasts through ICAM-1/lymphocyte function-associated antigen 1 interactions. beta 1 and beta 2 integrins, ICAM-1, and endothelial leukocyte adhesion molecule 1 all may be involved in the homing of lymphocytes to involved skin in patients with systemic sclerosis.
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PMID:Immunologic aspects of scleroderma. 145 82

Scleroderma fibrotic lesions demonstrate vascular disease, mononuclear cell infiltrates, and increased collagen. Fibroblasts in these lesions are activated to synthesize increased extracellular matrix substances, a phenotype that continues when these cells are removed and grown in tissue culture. Levels of messenger RNA for connective-tissue substances, measured directly in biopsies of scleroderma skin, show increased message for type I collagen, but not type III collagen or fibronectin. Increased procollagen type I in scleroderma skin occurs in the papillary dermis, perivascular areas, and deep interstitium, even in skin areas that are not yet fibrotic. Scleroderma fibroblasts express more intercellular adhesion molecule 1 on their surfaces than do normal cells, and this molecule is increased in endothelial cells, mononuclear cells, and fibroblasts. In vitro scleroderma fibroblasts adhere more frequently to extracellular matrix substances and retract collagen lattices to a greater extent. Peripheral blood lymphocytes from scleroderma patients produce excessive amounts of interleukin-2 when incubated with type I collagen, and circulating basophils release more histamine than do normal cells. There is evidence for activated eosinophils both in the dermis and pulmonary lesions in scleroderma, which may play a role in fibrosis. Transforming growth factor-beta is overexpressed by alveolar macrophages from patients with fibrotic pulmonary disease. Scleroderma fibroblasts, when exposed to transforming growth factor-beta, overexpress the alpha-type receptor for platelet-derived growth factor. Scleroderma sera more frequently contain measurable quantities of interleukin-4, interleukin-6, and interleukin-2. Interleukin-4 causes adult dermal fibroblasts to proliferate and to make interleukin-6. Interleukin-6 has been shown to stimulate fibroblast synthesis of collagen and glycosaminoglycans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Connective tissue metabolism including cytokines in scleroderma. 145 83

Rheumatoid synovial T lymphocytes were investigated for the presence of mRNA for the cytokines interleukin-2, -3, -4, -6, interferon-gamma, the interleukin-2 receptor (CD25) and the proto-oncogene c-myc. The isolated RNAs were analysed by dot blot and Northern blot hybridization. Our results show that synovial T lymphocytes from patients with rheumatoid arthritis (n = 12) had spontaneous in vivo gene transcription of interleukin-2 (93%), interleukin-4 (67%), interleukin-6 (92%), interleukin-2 receptor (92%) and the proto-oncogene c-myc (67%). Only a few of the RA patients had synovial T cells with increased expression of mRNA for interleukin-3 (25%) and interferon-gamma (25%). The amounts of mRNA for the various cytokines and activation molecules produced by the rheumatoid synovial T lymphocytes were in most instances comparable to those of normal peripheral blood T lymphocytes activated in vitro by the mitogen phytohaemagglutinin. The data thus indicate that the synovial T lymphocytes are activated in vivo in the majority of rheumatoid arthritis patients.
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PMID:Spontaneous in vivo gene transcription of interleukin-2, interleukin-3, interleukin-4, interleukin-6, interferon-gamma, interleukin-2 receptor (CD25) and proto-oncogene c-myc by rheumatoid synovial T lymphocytes. 146 23

Cytokines are known to play an important role in host defense by regulating the function, growth, and differentiation of the cells of the immune system. We hypothesize that, in the tumor microenvironment, tumor cells and resident tissue cells (e.g., fibroblasts) also produce cytokines that may regulate the local immune response to tumors. Initially, homogenates of eight head and neck squamous cell carcinomas (HNSCC) were assayed for the presence of interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) to establish the presence of these cytokines in the tumors in vivo. We detected IL-1 in all tumor homogenates and IL-4, IL-6, and GM-CSF in some homogenates. To assess the ability of HNSCC to produce these cytokines, supernatants of short-term primary cultures of HNSCC were assayed for the same cytokines. No IL-1 was detected, although baseline levels of IL-4, IL-6, and GM-CSF were present. However, the stimulation of primary tumor cultures with exogenous IL-1 induced or significantly enhanced production of IL-4 (p < 0.01), IL-6 (p < 0.001), and GM-CSF (p < 0.02). These results support our hypothesis that HNSCC secrete cytokines that may influence the response of local immune cells. Our data also suggest that IL-1 may have a central role in regulating the local immune response through the enhancement or induction of cytokine production by tumor and/or resident tissue cells.
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PMID:Cytokine expression by head and neck squamous cell carcinomas. 146 1

Our results indicate that ST 789 exhibits complex immunomodulant properties. In fact, we found that ST 789 inhibits the expression of activation antigens, such as interleukin-2 and transferrin receptors by peripheral blood mononuclear cells (PBMCs) from healthy subjects following mitogen stimulation, but we were not able to detect under the same experimental conditions any effect on the in vitro production of soluble CD8 antigen and of interleukin-4 as well as on the proliferative response of antigen-specific and autoreactive human T cell lines. Finally, we showed that ST 789 is able to strongly enhance the in vitro production of interleukin-6 by PHA-stimulated PBMCs. The reduced expression of activation antigens in the presence of ST 789 does not seem to be mediated by CD8+ suppressor T lymphocytes, as indicated by the normal soluble CD8 levels in culture media, but rather reflects a direct inhibitory action on T helper proliferation and likely on interleukin-2 secretion. The strong enhancement by ST 789 of the in vitro interleukin-6 production seems to indicate the most relevant possibility of clinical applications in human diseases.
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PMID:Modulation by ST 789 of in vitro lymphocyte activation and cytokine production. 158 23

Glucocorticoid hormones, calcium ionophores and anti-CD3 monoclonal antibodies induce apoptosis in mouse thymocytes. This type of cell death, which is characterized by an extensive DNA fragmentation into oligonucleosomal subunits, occurs in the intrathymic process of negative selection, and is involved in the deletion of autoreactive T-cells during thymic maturation. A number of cytokines are able to modulate apoptosis, and interleukins, including interleukin-1, interleukin-2, and interleukin-4, play a crucial role in thymic maturation and T-cell development. We tested the effects of several cytokines on the glucocorticoid hormone-induced apoptosis of mouse thymocytes in vitro, and demonstrated that interleukin-1 alpha, interleukin-2, and interleukin-4 inhibit the apoptosis induced by dexamethasone, but that interleukin-3 and interleukin-6 exert no noteworthy effect. Dose-response experiments indicated that interleukin-4 is more potent than interleukin-1 alpha and interleukin-2 in inhibiting dexamethasone-induced apoptosis. Furthermore, interleukin-4 fully inhibited the DNA fragmentation induced by the protein kinase-C activator 12-O-tetradecanoylphorbol-13-acetate, but was ineffective against apoptosis induced by the calcium ionophore A23187. These results suggest that interleukins regulate the thymic selection process by acting as modulators of the negative selection process.
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PMID:Interleukins modulate glucocorticoid-induced thymocyte apoptosis. 159 84


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