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 nature of the events that precipitate autoimmune diseases varies. Interleukin-1 and tumor necrosis factor do not precipitate autoimmune diseases but rather act as effector molecules. They induce eicosanoid and nitric oxide synthesis, stimulate collagenases and collagen synthesis, and trigger the genes for other cytokines, namely interleukin-2, interleukin-6 and interleukin-8. The ability to block interleukin-1 with the receptor antagonist, and tumor necrosis factor with soluble receptors, has given investigators specific tools to test the role of these two cytokines in the pathological processes of autoimmune disease.
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PMID:Inflammatory cytokines: interleukin-1 and tumor necrosis factor as effector molecules in autoimmune diseases. 166 33

Increased interleukin-6 levels in culture media of mitogen-driven non adherent peripheral blood mononuclear cells were measurable in patients with monoclonal gammapathies of unknown significance but not in patients with multiple myeloma, indicating that in the former circulating mononuclear cells other than monocytes are involved in producing interleukin-6. Increased interleukin-4 levels were detected in supernatants of mitogen-driven peripheral blood mononuclear cells from patients with monoclonal gammapathies of unknown significance and from patients with multiple myeloma. The further increased interleukin-4 content in supernatants of non adherent cell cultures of multiple myeloma patients only suggests a somewhat inhibitory role of monocytes on interleukin-4 production, at least in multiple myeloma. Undetectable interleukin-2 levels in culture media were found in patients with monoclonal gammapathies of unknown significance and in patients with multiple myeloma. Serum levels of interleukin-6 and interleukin-2 were not measurable in either group, and interleukin-4 was detected only in a few patients. Our study suggests that in monoclonal gammapathies peripheral blood mononuclear cells could participate in producing cytokines involved in the regulation of B lymphocyte proliferation and differentiation. However, the pathophysiologic role in these patients of IL-6 and IL-4 in vitro, and possibly in vivo, produced by circulating lymphocytes remains to be established.
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PMID:Cytokine production in patients with monoclonal gammapathies. 166 21

The activity of lymphokine-activated killer (LAK) cells is supported by various cytokines. The objective of this study was to see if recombinant interleukin-6 (IL-6) either alone or in combination with interleukin-2 (IL-2) has any effect on the generation of LAK cells. Peripheral blood mononuclear cells of healthy donors were cultured for 4 or 6 days with both cytokines either alone or in combination. LAK activity against K562 and natural killer-resistant Daudi cells was assessed by a 4-h and an 18-h 51Cr-release assay at various effector to target ratios. IL-6 alone in increasing concentrations did not induce LAK cell activity. Neither additive nor synergistic effects of IL-6 with IL-2 were observed. Immunofluorescence analysis with phycoerythrin-conjugated anti-CD56 antibody demonstrated that IL-6 could not maintain or increase the number of CD56-positive cells over a 6-day culture period. These results suggest that IL-6 does not support LAK cell generation by itself or increase LAK cell activity in combination with IL-2.
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PMID:Interleukin-6 does not support interleukin-2 induced generation of human lymphokine-activated killer cells. 171 37

This study examined the influence of cytokines on substance P (SP) receptors (NK1 subtype) in the human astrocytoma cell line UC11. Following trypsinization and passage, the density of SP receptors in these cells was rather low but gradually increased several fold over the course of a few days in culture. Frequent replacement of the growth medium enhanced the density of receptors even more, suggesting that growth factors in the culture medium may determine the levels of receptor. Exposure of the cells to sub-nanomolar concentrations of tumor necrosis factor (TNF alpha) or interleukin-1 beta (IL1 beta), but not interleukin-2 or interleukin-6, decreased the density of SP receptors. This was accompanied by a decrease in the ability of SP to stimulate inositolphosphate formation. The ability of histamine to activate inositolphosphate formation was not influenced by the cytokines. The decrease in SP receptor density was readily reversible on washout of the cytokines. The EC50 for TNF alpha was approximately 0.5 ng/ml, the EC50 for IL1 beta was approximately 0.1 ng/ml. Radioligand binding studies with [125I]TNF alpha indicated the presence of a low density of high affinity binding sites for this ligand: Kd = 2.5 +/- 0.6 ng/ml, Bmax = 14.8 +/- 2.7 fmol bound/mg protein (assuming trimeric form of ligand bound). The most likely explanation for the cytokine effect is an inhibition of the synthesis of new receptors.
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PMID:Tumor necrosis factor and interleukin-1 down-regulate receptors for substance P in human astrocytoma cells. 172 42

In order to better understand the regulation of CD14 antigen on the surface of the monocyte-like cell line U937 in response to bacteria, the expression and regulation of CD14 antigen on these cells when cultured with formalin-killed bacteria were determined using the monoclonal antibody MY-4 and analyzed by means of the indirect immunofluorescence method. CD14 expression was induced on the U937 cells after about 48 hours of culture with all of the formalin-killed Gram-negative bacteria used in this study but with none of the Gram-positive bacteria. Maximum expression was obtained after culture with formalin-killed Salmonella enteritidis strain 116-54. Various cytokines such as interleukin-1 beta, interleukin-2, interleukin-6, interferon-gamma and tumor-necrosis factor-alpha were assayed in the culture supernatant of U937 cells cultured with or without formalin-killed Salmonella enteritidis 116-54 using an enzyme-immunoassay or radioimmunoassay system. The U937 cells were found to produce a large amount of interleukin-6 in response to formalin-killed Salmonella enteritidis 116-54. On the other hand, culture supernatant (referred to as conditioned medium) obtained from the U937 cells after 72 h of culture with formalin-killed Salmonella enteritidis 116-54 also induced strong expression of CD14 antigen 48 to 72 h later, and this was blocked by the addition of anti-human interleukin-6 antibody. These findings suggest that the expression of CD14 antigen on the surface of U937 cells cultured with formalin-killed Gram-negative bacteria is induced by interleukin-6 and can be explained on the basis of the autocrine mechanism of interleukin-6.
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PMID:Induction of CD14 antigen on the surface of U937 cells by an interleukin-6 autocrine mechanism after culture with formalin-killed gram-negative bacteria. 172 78

The leukemic T-cells of the six patients with T-cell chronic lymphocytic leukemia (T-CLL), four with CD4 and CD45R-positive (CD4+ CD45R*) T-CLL and two with CD8 and CD45R-positive (CD8+ CD45R+) T-CLL phenotype were studied for detailed immunologic phenotypic and functional characteristics. The levels of soluble interleukin-2 receptors were elevated significantly in the serum of all four patients with CD4+ CD45R+ T-CLL. Moreover, the CD4+ CD45R+ T-CLL patients' T-cells, after in vitro stimulation with phytohemagglutinin and concanavalin A, expressed elevated percentages of interleukin-2 receptors on cells and secreted high interleukin-2 activity. The B-cell growth factor (BCGF) activity from three patients with CD4+ CD45R+ T-CLL was enhanced, but B-cell differentiation factor (BCDF) activity of the all T-CLL patients was decreased. Reduced BCGF and BCDF activity of the leukemic T-cells was one possible mechanism of hypogammaglobulinemia detected in two patients with T-CLL. All T-CLL patients' leukemic T-cells had diminished immunoregulatory functional activity in allogeneic mixed lymphocyte reactions. These observations suggest that leukemic T-cells from T-CLL patients have many immunologic functional defects that may be important in their proliferative potential.
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PMID:T-cell chronic lymphocytic leukemia. T-cell function and lymphokine secretion. 173 13

A number of in vitro studies suggest an immunoregulatory role of 1 alpha,25 Dihydroxyvitamin D3 (1,25-(OH)2D3). The hormone inhibits production of interleukin-2 and immunoglobulin, and it blocks lymphocyte proliferation. Diverse effects on monocyte functions have been reported. However, immunological effects of 1,25-(OH)2D3 have not been substantiated in vivo. Six healthy male volunteers, aged 28-45 yr, were treated orally with 1,25-(OH)2D3 (tabl. Rocaltrol), 1 microgram twice daily for 7 days. Blood and urine samples were collected before and 7 days after initiation of treatment. Blood mononuclear cells from individuals treated with 1,25-(OH)2D3 showed a significantly reduced production of both interleukin-1 alpha (45%) and tumor necrosis factor-alpha (58%) (both measured by ELISA). Interleukin-6, production, measured by the B9 cell assay, was reduced in five individuals (78%), and unchanged in one. There was no effect on the release of interleukin-1 beta. There was no measurable effect on interleukin-2, interferon gamma or immunoglobulin production, or on mitogen-induced proliferation of blood mononuclear cells. Serum-osteocalcin and urine excretion of calcium were increased to 131 and 173%, respectively. The serum-calcium and serum-phosphate levels were unchanged.
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PMID:Down-regulation of monocyte functions by treatment of healthy adults with 1 alpha,25 dihydroxyvitamin D3. 178 65

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of unknown etiology. They are characterized by an activation of intestinal mononuclear cells. Cytokines play a crucial role in the regulation of the functions of these cells. An increased synthesis of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha), which are primarily synthesized by activated monocytes/macrophages has been described in patients with IBD. The synthesis of interleukin-2 (IL-2) and of interferon gamma (IFN gamma), which are produced by lymphocytes, on the other hand, has been found to be decreased. The published data are, however, not quite consistent. In patients with IBD there is not only a stimulation of the local cytokine production in the gut. The blood levels and the synthesis of the cytokines IL-1, IL-6 and TNF alpha by peripheral blood mononuclear cells are also increased, in particular in patients with Crohn's disease. Drugs, which are commonly used for the treatment of IBD impair the synthesis of these cytokines in monocytes/macrophages.
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PMID:Inflammatory mediators in chronic inflammatory bowel diseases. 179 95

B lymphocytes from patients with systemic lupus erythematosus (SLE) secreted high levels of immunoglobulin spontaneously when cultured in vitro. Addition of the cytokines interleukin-2, interleukin-4 and interleukin-6 either alone or in combination failed to augment spontaneous immunoglobulin synthesis. Percoll-separated low-density SLE B lymphocytes matured into immunoglobulin-secreting cells also independent of exogenous interleukins. During maturation these cells became enlarged and less dense, and began to express CD23. This was in contrast to normal B cells, which did not secrete immunoglobulin spontaneously but synthesized IgM after interleukin stimulation. These results indicate that in vitro immunoglobulin synthesis by SLE B cells is already initiated in these cells and progresses independently of further stimulatory manoeuvres.
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PMID:Cytokine-independent progression of immunoglobulin production in vitro by B lymphocytes from patients with systemic lupus erythematosus. 182 87

Recent studies demonstrate that several cytokines are potent modulators of steroid release from the testis. In an attempt to determine whether these agents may influence other types of secreted substances, we used plaque assays to measure the effect of interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor alpha on transferrin (TF) release from Sertoli cells in culture. Because Sertoli cells from different parts of the tubule respond differently to modulatory factors, we used cultures obtained by microdissection from stages III-V, VII, IX-XI, and XIII of the cycle of the seminiferous epithelium. Our results revealed that each agent increased the rate of TF plaque formation from cultures of IX-XI, and XIII staged segments but not from those staged III-V and VII. Moreover, IL-6, but not the other cytokines, modified the response of Sertoli cells to another regulator, FSH. This was evidenced by our findings that pretreatment with IL-6 for 1 h resulted in FSH-induced increases in the rate of plaque formation for cells from IX-XI segments, in addition to those segments which are normally responsive without pretreatment (III-V and VII segments). Further experiments revealed that IL-6 also had a chronic influence on the proportion of TF secretors present in certain staged cultures. Treatment for 24 h with IL-6 markedly reduced the percentage of TF secretors in cultures from stage XIII segments and resulted in a slight increase in TF cells for stage VII cultures. However, no chronic influences in TF secretors were detected with either IL-2 or tumor necrosis factor alpha treatment. Our results demonstrate very clearly that certain cytokines acting in a stage specific manner have acute and/or chronic influences on the release of TF from Sertoli cells. These findings, when viewed in light of reports of the presence of these factors in the testis, suggest strongly that cytokines or cytokine-like substances, by modulating the release of Sertoli cell substances, may play an important role in testis function.
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PMID:Effects of interleukin-6, interleukin-2, and tumor necrosis factor alpha on transferrin release from Sertoli cells in culture. 190 26


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