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)

Tumor necrosis factor receptor p75 (TNF-R p75) is a 75-kDa type I transmembrane protein expressed predominantly on cells of hematopoietic lineage. TNF-R p75 belongs to the TNF receptor superfamily characterized by cysteine-rich extracellular regions composed of three to six disulfide-linked domains. In the present report we have characterized, for the first time, the complete gene structure for human TNF-R p75, which spans approximately 43 kbp. The gene consists of 10 exons (ranging from 34 base pairs to 2.5 kilobase pairs) and nine introns (343 base pairs to 19 kilobase pairs). Consensus elements for transcription factors involved in T cell development and activation were noted in the 5'-flanking region including T cell factor-1, Ikaros, AP-1, CK-2, interleukin-6 receptor E (IL-6RE), ISRE, GAS, NF-kappaB, and Sp1. The unusual (GATA)n and (GAA)(GGA) repeats found within intron 1 may prove useful for further genome analysis within the 1p36 chromosomal locus. Characterization of the human TNF-R p75 gene structure will permit further assessment of its involvement in normal hematopoietic cell development and function, autoimmune disease, and nonrandom translocations in hematopoietic malignancies.
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PMID:Human tumor necrosis factor receptor p75/80 (CD120b) gene structure and promoter characterization. 870 85

Systemic lupus erthematosus (SLE) has been very often associated with complication in reproduction. 29 SLE women divided into two groups A (10 patients aged 18-36 years) and B (19 patients aged 42-67 years) were queried with regard to general, obstetric and SLE history by the use of a questionnaire. Serum of each patient was tested for interleukin-6 (by ELISA), sperm antibodies (by mixed antiglobulin reaction and tray agglutination test) and zona pellucida antibodies (passive haemagglutination test and ELISA methods). Neuropathic, cutaneous and nephrotic symptoms prevailed in the SLE women. The group of younger women showed significant problems in fertility (only one woman became a happy mother) while 15 women in the elderly group were successfully pregnant before SLE diagnosis. Low serum II-6 levels were detectable only in 3 cases as a possible consequence of corticoid treatment. Levels of zona pellucida antibodies were higher in the elderly group B, levels of sperm antibodies were higher in contrast to younger SLE women (group A). The laboratory findings may be related to the severity of autoimmune disease and to menopause onset (group B) or good sexual activity (group A).
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PMID:Systemic lupus erythematosus in women and serum interleukin-6, sperm and zona pellucida antibodies. 876 1

Rheumatoid arthritis (RA) has no firm etiologic basis. It progresses as an autoimmune disease and evolves into a chronic inflammatory joint disease complicated by recurrent episodes of systemic acute-phase reactions, which sometimes result in amyloidosis. Cytokines play a pivotol role in inflammation and the immune response. Proinflammatory cytokines such as interleukin-1, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 are present at high levels in arthritic joints, and their blood concentration correlates with the severity of the RA. Some of the activities of the proinflammatory cytokines, such as stimulation of leukocyte infiltration and release of their proteolytic enzymes, may be mediated by acute phase proteins (APPs), such as C-reactive protein and serum amyloid A, and by chemokines such as interleukin-8. Cytokines, chemokines, and APPs reciprocally regulate each others' expression and activities, constituting a communication network between fibroblasts, macrophages, lymphocytes, and hepatocytes. Activation of the network results in inflammation and the progressive destruction of joints and systemic symptoms characteristic of RA.
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PMID:Role of cytokines, acute-phase proteins, and chemokines in the progression of rheumatoid arthritis. 891 97

In a continuous one-bottle sucrose intake test, 4-month-old autoimmune MRL-Ipr mice show a shift to the right along the X-axis of the concentration-intake function, compared to congenic MRL +/+ controls. Using a brief (60-min) and a continuous (48-h) two-bottle test, the present report examines potential factors that could account for the reduced responsiveness to a palatable stimulus. Study 1 examines whether preference for sucrose is associated with age, changes in food/water intake, or impaired renal function. Reduced preference for sucrose was observed in 5-6-week-old MRL-Ipr males, although food/water intake or blood creatinine levels did not differ from control values. Immunosuppressive treatment abolished this deficit, suggesting a role of immune factor(s). Study 2 tests the hypothesis that chronic upregulation of the neuroactive cytokine interleukin-6 (IL-6), reported to occur from 3 weeks of age in young MRL-Ipr mice, reduces preference for sucrose. Sustained administration of IL-6 was produced by infecting healthy MRL +/+, C3H.SW and Balb/C mice with adenovirus vector carrying cDNA for murine IL-6. This resulted in high serum IL-6 levels over 5 days, a rapid decline in preference for sucrose and low blood glucose levels. The results from Study 1 indicate that impaired sensitivity to sucrose in MRL-Ipr mice can be detected before autoimmune disease is florid in MRL-Ipr mice. The results from Study 2 are consistent with altered motivation/emotional states after infection, and point to sustained IL-6 production as an early mechanism in behavioral alterations during chronic autoimmune/inflammatory conditions.
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PMID:Reduced preference for sucrose in autoimmune mice: a possible role of interleukin-6. 929 5

Interleukin-10 is an important cytokine that is involved in regulation of pro-inflammatory cytokines and T-cell responses. Interleukin-10 has been studied extensively in various preclinical and clinical models of inflammation. The most remarkable and consistently reproducible quality of IL-10 is its ability to downregulate macrophage functions. This includes inhibiting the production of pro-inflammatory cytokines such TNF-alpha, Interleukin-1, Interleukin-6 and antigen presentation by these professional antigen presenting cells. Additionally, Interleukin-10 also has effects on various other cell types of hematopoietic origin such as B-cells, neutrophils, and most importantly T-cells. Interleukin-10 has shown efficacy in several models of autoimmune disease. The present article deals with the effect of Interleukin-10 in animal models of inflammatory bowel disease and the results of phase I clinical trials in normal human volunteers and chronic active Crohn's disease patients.
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PMID:Immunomodulation of Crohn's disease by interleukin-10. 942 29

Thyroid autoimmune reactions start with an accumulation of mainly dendritic cells in the thyroid. There is increasing evidence that, apart from being antigen-presenting cells, they are also able to control the growth and hormone synthesis of neighbouring endocrine cells. The questions thus arise: are dendritic cells accumulating in the pre-autoimmune thyroid in response to an altered proliferative or metabolic activity of thyrocytes, and do cytokines, monocyte chemoattractants, or both, have a role in their accumulation? We have investigated these questions in thyrocytes of the biobreeding diabetes-prone (BB-DP) rat in relation to the start of the intrathyroid accumulation of dendritic cells--that is, at about 9 weeks of age. BB-DP rats and Wistar rats (controls) were studied from 3 to 20 weeks of age. Hyperplastic goitre development was studied by assessing the thyroid weight and by measuring the number of thyrocyte nuclei per 0.01 mm2 thyroid section. In addition, the in situ expression of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), monocyte-chemotactic protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were studied by immunohistochemistry. The in vitro proliferative capacity of BB-DP and Wistar thyrocytes was measured by tritiated-thymidine ([3H]TdR) and bromodeoxyuridine (BrdU) incorporation into reconstituted, TSH- and non-TSH-stimulated, cultured thyroid follicles. Further in vitro studies consisted of measurement of the production of thyroxine (T4), triiodothyronine (T3), thyroglobulin, IL-6, TNF-alpha and MCP-1 by the thyroid follicles. BB-DP rats developed a small hyperplastic goitre between the ages of 9 and 12 weeks. The in vitro proliferative rate of thyrocytes isolated from hyperplastic BB-DP thyroids was significantly lower than that of Wistar thyrocytes. This phenomenon also occurred in follicles isolated from BB-DP rats before hyperplastic goitre development, which produced significantly less T4, but more T3, than did Wistar follicles of the same age. At the time of and after hyperplastic goitre development, BB-DP follicles exhibited altered metabolic behaviour and produced significantly more T4, but equal amounts of T3 compared with both Wistar follicles of the same age and follicles of younger BB-DP rats (both under basal conditions and TSH-stimulated). In vitro IL-6 production by these BB-DP thyroid follicles was also increased. There was no noteworthy difference in production of thyroglobulin and MCP-1 between BB-DP and Wistar follicles at any age. TNF-alpha was not produced by BB-DP or Wistar thyroid follicles. Immunohistochemistry revealed the expression of IL-6 by both BB-DP and Wistar thyroid follicle cells at all times of sampling. MCP-1 and TNF-alpha were expressed only when infiltrates were present in BB-DP thyroids (restricted to leucocytes, ages > 18 weeks). Modest ICAM-1 expression was restricted to large blood vessels in both BB-DP and Wistar thyroids; in the case of infiltrates (BB-DP rat) alone, high ICAM-1 expression was found on blood vessels and leucocytes in these infiltrations. At the time of intrathyroidal dendritic cells accumulation, BB-DP rats develop a small hyperplastic goitre. At that time there is also in vitro evidence for a shift to a higher production of thyroxine and IL-6 from thyrocyte follicles. The in vitro proliferation rate of BB-DP thyrocytes is, however, abnormally low (both in the pre- and hyperplastic period). Similar pre-autoimmune thyroid growth abnormalities have been described in another animal model of thyroid autoimmune disease, the obese strain chicken.
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PMID:Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response. 961 56

1,25-dihydroxyvitamin D3 (1,25-D3) modulates lymphocyte and macrophage functions in vitro. These effects are exerted through production of 1,25-D3 by antigen-presenting monocytes/macrophages (MO) and binding to vitamin D receptors expressed in MO and in activated, but not in resting T-lymphocytes. 1,25-D3 inhibits production of MO-derived cytokines such as interleukin-1 alpha, interleukin-6, and tumor necrosis factor alpha at the post-transcriptional level, most likely by reducing the half-life of specific mRNAs. The proliferation of T-cells and their release of cytokines such as IL-2 and interferon gamma are also suppressed by 1,25-D3, partly as a result of the reduced production of T-cell-activating cytokines (interleukin-1 alpha, tumor necrosis factor alpha), but also because of a direct effect on the T-cells. Although 1,25-D3 has no apparent effect on B-lymphocytes, the T-cell suppression indirectly inhibits antibody production by B-cells. The CD45R0+ subset of T-helper cells is relatively more sensitive than the CD45RA+ subset to the inhibitory effects of 1,25-D3. The CD45R0+ subset plays a key role in immune activation and in the pathogenesis of many autoimmune disease. 1,25-D3 acts as an important local regulator of T-cell functions and thus modulates several immunological effector functions. The actions of 1,25-D3 are distinct from those of commonly used immunosuppressants, and vitamin D3 analogs are therefore potentially useful as alternatives to conventional immunosuppressive therapies.
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PMID:1,25-Dihydroxyvitamin D3 as a natural regulator of human immune functions. 962 96

Treatment of human peripheral blood lymphocytes (PBL) in vitro with the cytokine interleukin-6 (IL-6) induces increased levels of the 90 kDa heat shock protein (hsp90). Hsp90 levels are also elevated in PBLs of human patients with systemic lupus erythematosus (SLE) and in MRL/lpr mice with autoimmune disease. Although IL-6 is elevated in both these situations it has not been shown that it is involved in stimulating elevation of hsp90 levels in vivo. Here we show directly that the elevation of IL-6 in vivo either in mice transgenic for the IL-6 gene or in knock-out mice lacking a functional gene for the transcription factor C/EBP beta (NF-IL-6) does indeed result in elevated hsp90 levels. This overexpression is associated with the specific production of autoantibodies to hsp90 in these mice which is also observed in SLE patients and MRL/1pr mice. Hence IL-6 is likely to play a critical role in the regulation of hsp90 levels both in autoimmune disease states and potentially in normal cells in vivo. In turn the elevated levels of hsp90 produced in autoimmune diseases are likely to be responsible for the observed production of anti-hsp90 autoantibodies.
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PMID:Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDa heat shock protein (hsp90) and the production of anti-hsp90 antibodies. 969 73

Myasthenia gravis (MG) is a T-cell-dependent and antibody-mediated autoimmune disease of the neuromuscular junction, in which the cytokine network may be deranged. Specific receptors for interleukin (IL)-6, a cytokine with several effects on the neuroimmune system, have been found on human lymphocytes. The aim of the present study has been to assay IL-6 binding on peripheral blood T cells from MG patients. We found that T cells from MG patients have significantly more IL-6 receptors than those from controls (Bmax: 334 +/- 6 vs 251 +/- 4 (mean +/- SEM) receptors/cell). Such IL-6 binding sites are of the same type in patients and healthy subjects (Kd: 26.5 +/- 0.7 vs 25.7 +/- 0.9 (mean +/- SEM) pM). The enhanced T-cell interleukin-6 binding is due to an increased number of interleukin-6 receptors on T-helper lymphocytes. These results are discussed in terms of MG immunopathogenesis, since it has been reported that activated T cells have increased amounts of IL-6 receptors.
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PMID:T-cell interleukin-6 receptor binding in patients with myasthenia gravis. 970 94

Elevated concentrations of plasma proinflammatory cytokines have been detected in patients with alcoholic hepatitis (AH) and in a model of lipopolysaccharide-induced hepatitis in ethanol-fed Wistar rats. These cytokines have been implicated in the pathogenesis of the liver damage. Considering the likely involvement of the immune system in AH, and the frequent use of Lewis rats in autoimmune disease models, Lewis rats were examined in the model to determine whether they would more closely mimic the immune status of a chronic alcoholic and be a preferable strain for use in future experiments. Lipopolysaccharide-induced hepatic tumor necrosis factor-alpha, interleukin-1alpha, interleukin-1beta, and interleukin-6 mRNA expression was examined in both rat strains. The overall pattern of histological (panlobular piecemeal necrosis) and biochemical liver damage (plasma ALT levels), and cytokine expression was similar in both strains. Thus, it would appear that, despite the known susceptibility of Lewis rats to autoimmune phenomena, they do not respond to the experimental regime significantly better than Wistar rats. This study confirms that unknown mediators are contributing to the liver damage seen in this model and possibly in AH.
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PMID:A comparison of lipopolysaccharide-induced hepatitis in ethanol-fed Wistar and Lewis rats. 980 38


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