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)

Only a minority of T cells at cell-mediated immune lesions are antigen specific. In the lesions of human autoimmune disease, such as the synovial membrane in rheumatoid arthritis, the T cells are activated as shown by a variety of phenotypic and functional changes including the expression of HLA-DR and the production of interleukin-6 (IL-6). The stimulatory pathway involved is unknown but does not seem to involve the T-cell receptor. Alternative pathways of activation which may be involved include the CD2 molecule. It is shown that the formation of sheep red blood cell (SRBC) rosettes with resting T cells from human peripheral blood, which is equivalent to CD2/LFA-3 binding, leads to the de novo transcription of the HLA-DR and IL-6 genes and the expression of HLA-DR on the surface of the T cells. There was no transcription of the interleukin-2 (IL-2) or the interleukin-2 receptor (IL-2R) genes and Tac expression was not seen. The rosetted T cells did not proliferate. These are all characteristics of T cells at chronic inflammatory sites. It is concluded that receptor-ligand interactions between CD2/LFA-3, which are expressed in increased amounts in the rheumatoid joint, may be one pathway by which antigen non-specific T cells are recruited as effector cells in lesions of human autoimmune disease.
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PMID:Activation of HLA-DR and interleukin-6 gene transcription in resting T cells via the CD2 molecule: relevance to chronic immune-mediated inflammation. 135 12

Chronic urticaria remains one of the major unsolved clinical problems in dermatology. My group has employed an integrated experimental approach in order to shed light on the pathophysiology and treatment of this group of disorders. Using delayed pressure urticaria as a model, evidence has emerged of the role of eosinophil major basic protein (MBP) and of interleukin-6 (IL-6) as important molecular mediators, possibly explaining the poor response to H1 antihistamines. Our recent work in chronic idiopathic urticaria has led to identification of a circulating greater than 100 kD factor which causes wealing following intradermal injection and which releases histamine from normal leukocytes in vitro. Further characterisation confirmed that this skin and histamine releasing reactivity is due mainly to an IgG anti-IgE autoantibody. That this autoantibody is functionally significant is supported not only by its ability to release histamine and cause local wealing, but also by the results of removal by plasmapheresis which we have shown to cause clinical improvement in seven out of eight patients with severe unremitting chronic urticaria. It is concluded that chronic 'idiopathic' urticaria is an autoimmune disease due, in most patients, to a functionally significant IgG anti-IgE autoantibody. Immunotherapy offers the best long-term prospects of relief in severe unremitting cases.
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PMID:Urticaria: new molecular insights and treatments. The Parkes Weber Lecture 1991. 137 92

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

The effects of SM-8849 on the development of autoimmune disease in MRL/Mp-1pr/1pr mice were examined. SM-8849 improved survival as well as renal disease, restored the deficits in splenic cell responsiveness to stimulation by mitogens or conventional antigens, and prevented lymphadenopathy and splenomegaly coincident with a decrease in the number of Thy-1+/Lyt-2-/L3T4- cells. SM-8849 also suppressed the production of the B-cell differentiation factor, possibly with a resulting preferential reduction of autoantibodies. In addition, SM-8849 depressed the production of hydrogen peroxide from macrophages. These results suggest that the administration of SM-8849 to a subject with autoimmune diseases can induce immunological improvements with possible clinical effectiveness.
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PMID:Alteration in progression of murine autoimmune disease by treatment with a novel immunomodulator, SM-8849. 178 57

This study demonstrates that interleukin-6 (IL-6) increases the autoantibody production by B cells from NZB/W F1 mice. Splenic B cells were cultured for 5 days in the presence or absence of human IL-6, and then the anti-DNA antibody and immunoglobulin contents in the culture supernatants were measured by ELISA. Adding IL-6 increased IgG anti-DNA antibody production by B cells from old mice (30 weeks), but not from young ones (17 weeks). B cells obtained from both young and old mice produced IgM anti-DNA antibody, which increased when IL-6 was added. The increased anti-DNA antibody production was suppressed by anti-recombinant human IL-6 antibody to the background level, i.e. antibody contents in the absence of IL-6. In contrast, murine IL-5 did not increase IgG anti-DNA antibody production, although it promoted the production of IgM anti-DNA antibody. Furthermore, when IL-5 was added in combination with IL-6, there was an additive increase in IgM, but not in IgG anti-DNA antibody production. Similar results were obtained in the measurement of the immunoglobulin contents. These results suggest the possible role of IL-6 in the pathogenesis of autoimmune disease in NZB/W F1 mice.
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PMID:Possible role of IL-6 in pathogenesis of immune complex-mediated glomerulonephritis in NZB/W F1 mice: induction of IgG class anti-DNA autoantibody production. 208 90

We have previously reported that B cell abnormality in NZB/W F1 mice developed independently of thymus. Here we examined further whether B cells from NZB/W F1 mice respond to interleukin-6 (IL-6), a factor for terminal differentiation of B cells. When freshly isolated splenic B cells were incubated for 5 days in the presence of human IL-6, an increased production of both IgM and IgG, including anti-DNA antibody, was evident in NZB/W F1 mice; there was no increase in BALB/c mice. A magnitude of augmentation in IgG but not IgM production by IL-6 became more apparent in older NZB/W F1 mice. The increased immunoglobulin production seen with IL-6 was neutralized by treatment with rabbit anti-recombinant human IL-6 antibody. As B cells from athymic NZB/W F1 nude mice also responded to IL-6, it was suggested that B cells in NZB/W F1 mice differentiated into the IL-6-responding state in a thymus-independent manner. This B cell abnormality may be associated with the pathogenesis of autoimmune disease in NZB/W F1 mice.
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PMID:Immunologic abnormality in NZB/W F1 mice. Thymus-independent expansion of B cells responding to interleukin-6. 226 91

Cytokines are a group of regulatory and immunomodulatory proteins involved in a number of physiological processes. Various disease states are believed to involve alteration of normal cytokine activity, including insulin-dependent diabetes mellitus, an autoimmune disease in which insulin secreting beta cells within pancreatic islets of Langerhans are selectively destroyed. Glucose-induced insulin secretion is inhibited by the cytokines interleukin-1 beta (IL-1 beta), interleukin-6 and tumour necrosis factor alpha (TNF) when combined with IL-1 beta in cultured rat islets, by IL-1 beta, TNF and interferon gamma in mouse islets, and by combined treatment of IL-1 beta, TNF and interferon gamma in human islets. Continued cytokine treatment in many cases leads to destruction of some, if not all, islet cells. A key factor in the inhibitory effect of IL-1 beta and TNF in rat islets is the generation of nitric oxide which inactivates enzymes such as aconitase and ribonucleotide reductase by formation of iron-nitrosyl complexes. This in turn may lead to reduced oxidation of glucose and synthesis of ATP and DNA respectively. The causes of cytokine-induced beta cell death are less well defined, but important factors may be nitric oxide-mediated DNA damage, depletion of NAD levels and toxic effects of oxygen free radicals and eicosanoids generated in addition to nitric oxide. Potentially important defence and repair responses induced by IL-1 beta treatment of rat islets are formation of heat shock protein, haem oxygenase, and superoxide dismutase. Other protective responses may be induction of cytokines and cytokine receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines, nitric oxide and insulin secreting cells. 775 73

Amiodarone, an iodine-rich cardiac drug, may induce thyrotoxicosis (AIT), which can occur in patients with preexisting thyroid abnormalities and in subjects with apparently normal thyroid glands. The pathogenesis of AIT is often due to iodine-induced excessive thyroid hormone synthesis, especially in patients with underlying thyroid disease. In some instances, however, AIT may be related to a destructive process due to amiodarone-induced thyroiditis, resulting in thyroid cell damage and thyroid hormone release into the circulation. Another thyroid inflammatory process, subacute thyroiditis, has been recently reported to be associated with markedly increased serum interleukin-6 (IL-6) levels. To investigate the significance of serum IL-6 levels in AIT, we evaluated in a cross-sectional study the following subjects: 27 AIT patients, 15 with no apparent thyroid abnormalities (AIT-) and 12 with nodular goiter and/or thyroid autoimmune disease (AIT+); 14 euthyroid patients receiving chronic amiodarone therapy; 10 patients with amiodarone-induced hypothyroidism; 56 patients with spontaneous hyperthyroidism due to Graves' disease (n = 35) or toxic adenoma/nodular goiter (n = 21); 20 subjects with nontoxic goiter; and 50 healthy controls. Serum free thyroid hormone concentrations did not differ in patients with amiodarone-induced or spontaneous hyperthyroidism. Mean (+/- SE) serum IL-6 values were as follows: AIT-, 573.5 +/- 78.7 fmol/L (range, 149.4-1145.1); AIT+, 152.7 +/- 46.3 fmol/L (range, < 25-505.6); euthyroid patients receiving chronic amiodarone therapy, 51.4 +/- 10.0 fmol/L (range, < 25-122.5); amiodarone-induced hypothyroidism, 43.8 +/- 8.4 fmol/L (range, < 25-84.3); Graves' disease, 108.2 +/- 18.2 fmol/L (range, < 25-250); toxic adenoma/nodular goiter, 97.6 +/- 10.3 fmol/L (range, < 25-168.9); nontoxic goiter, 47.3 +/- 7.1 fmol/L (range, < 25-106.6); and controls, 37.8 +/- 6.2 fmol/L (range, < 25-99.4). Serum IL-6 values in AIT- patients were markedly higher (P < 0.0001) than those in all other groups. Values in AIT+, although slightly higher, did not significantly differ from those in patients with spontaneous hyperthyroidism. AIT- patients had low 24-h thyroidal radioiodine uptake (RAIU), whereas AIT+ had inappropriately low normal to high (9-58%) RAIU values in the presence of excess iodine. The presence of markedly elevated serum IL-6 concentrations and low thyroidal RAIU values in patients with AIT without underlying thyroid disease suggests the presence of amiodarone-induced thyroiditis as the etiology of thyrotoxicosis. Treatment of 2 such patients with prednisone was associated with a dramatic reduction and prompt normalization of IL-6 and thyroid hormone values.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Serum interleukin-6 in amiodarone-induced thyrotoxicosis. 810 31

The characteristics of soluble interleukin-6 receptor (sIL-6R) in murine sera were examined. To investigate a relationship between serum sIL-6R level and autoimmune diseases, quantitative analysis of serum sIL-6R in MRL/lpr mice was performed by an enzyme-linked immunosorbent assay. The serum sIL-6R level in MRL/lpr mice of both sexes was below the detection limit (< 1.0 ng/ml) at 8 weeks of age, but it increased in accordance with age and reached 42 +/- 9.3 ng/ml in female and 31 +/- 13 ng/ml in male mice at 30 weeks of age. In MRL/+ mice, although an age-associated increase in serum sIL-6R level was observed, it was much less extensive than that in MRL/lpr mice. Elevated serum sIL-6R level at the age of 30 weeks was observed in female and male (NZB x NZW)F1 mice (32 +/- 10 ng/ml and 17 +/- 5.0 ng/ml, respectively), and male BXSB/Mpj Yaa mice (42 +/- 18 ng/ml), suggesting that elevated serum sIL-6R in aged mice is one of the characteristics of autoimmune-prone mice. Quantitative analysis of serum IL-6 in MRL/lpr revealed that the serum sIL-6R level correlated well with the serum IL-6 level. We also showed that sIL-6R in the sera from MRL/lpr mice could mediate the IL-6 functions through the IL-6 signal-transducing receptor component gp130, suggesting that elevated production of sIL-6R may partly contribute to development of autoimmune disease in MRL/lpr mice.
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PMID:Serum soluble interleukin-6 receptor in MRL/lpr mice is elevated with age and mediates the interleukin-6 signal. 847 2

Hairy cell leukemia is a uncommon B-cell chronic lymphoproliferative disease rarely associated with autoimmune phenomena. We present a positive CD 5 case with a positive antinuclear antibodies test in the absence of any relation to any other clinical autoimmune disease syndrome and we analyse the evolutive profile of serum concentration of several factors with prognostic significance, relating to the interferon alpha-2b treatment: C reactive protein, beta 2-microglobulin and erythropoietin presented at first very high basal levels that descended progressively until the last two normalized completely; the tumor necrosis factor-alpha manifested stable with normal values during the whole study; the gamma-interferon and interleukin-6 revealed a precocious increase at the start of the treatment later returning to their basal levels. These parameters may aid to assess the response to treatment in these patients.
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PMID:[Analysis of response to interferon alpha-2b and the significance of antinuclear antibodies in hairy cell leukemia]. 865 58


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