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)

In three experimental models in rats, surgical construction of a self-filling blind loop (SFBL), trinitrobenzene sulfonic acid (TNB) -induced colitis, and the combination of SFBL and TNB, the hypothesis was studied that intestine-derived endotoxins play a role in the pathogenesis of hepatobiliary disorders in chronic inflammatory bowel disease (CIBD). After eight weeks of treatment, a mild increase in portal and systemic endotoxin levels and interleukin-6 concentrations was observed and the serum levels of alkaline phosphatase, bilirubin, and ALAT were only mildly increased in SFBL plus TNB rats. Histopathological examination of the liver showed hardly any abnormalities in all three rat models. These results show that low-grade portal and systemic endotoxinemia in rats, induced by bacterial overgrowth and/or chemical colitis, is not able to induce hepatobiliary alterations. To exclude definitively a possible role for portal endotoxinemia in the pathogenesis of CIBD-associated hepatobiliary abnormalities, however, an adequate animal model for CIBD is urgently needed.
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PMID:Experimental colitis in rats induces low-grade endotoxinemia without hepatobiliary abnormalities. 820 Feb 52

To investigate the relationship between serum concentrations of interleukin-8 (IL-8) and disease activity in inflammatory bowel disease, serum IL-8 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in 93 patients. Interleukin-8 levels were compared with plasma interleukin-6 (IL-6) levels in 80 of these patients. Interleukin-8 levels were also measured in ten patients with active Crohn's disease, before and after treatment with a defined formula polymeric diet. Of these patients, 70 out of 93 IL-8 concentrations were below the detection limit of the assay. Levels were higher in patients with active ulcerative colitis (median < 20 pg/mL, 75th centile value = 190) compared with inactive disease (median and 75th centile value < 20; P < 0.05). Interleukin-8 concentrations correlated with a combined score for disease severity and extent (P = 0.01). Thirty-eight per cent (8/20) of patients with active Crohn's disease also had high levels of IL-8 but there was no significant difference between active and inactive disease. There was no correlation between serum IL-8 and plasma IL-6; on the contrary, very few patients had raised blood levels of both cytokines. In the diet treated group, serum IL-8 fell significantly after treatment (median = 37 pg/mL, range < 20-4615 before treatment, median < 20, range < 20-104 after treatment; P = 0.03). The results suggest that although IL-8 may be involved in the inflammatory process in inflammatory bowel disease, it is a poor marker of disease activity.
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PMID:Serum interleukin-8 in inflammatory bowel disease. 828 Aug 36

Acute phase proteins are released from the liver in response to cytokines, and measurement of serum concentrations offers a valuable means of assessing inflammatory bowel disease. C-reactive protein (CRP) is a participating prominent component of the acute phase response in active Crohn's disease. This study aimed at determining the comparative role of the cytokines interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6), in driving CRP production in inflammatory bowel disease, and to test the hypothesis that there is a difference in the profile of cytokines generated in these two conditions. Serum CRP, the release of the cytokines IL-1 beta and IL-6 from monocytes, and the ability of monocyte conditioned medium to stimulate CRP synthesis by hepatocytes in an in vitro system was measured in patients with ulcerative colitis and Crohn's disease. Monocytes from patients with Crohn's disease produced more 1L beta-1 than monocytes from patients with ulcerative colitis or normal controls. There was no increased tendency for monocytes from Crohn's disease patients to produce more 1L-6, so the greater circulating values of IL-6 reported by a number of authors in Crohn's disease may reflect the participation of a larger number of cells of the monocyte-macrophage series, or production of IL-6 by other cell types. Correlation of cytokine production by monocytes with in vitro CRP release from cultured hepatocytes in response to monocyte conditioned medium showed that, in that system, IL-1 beta was the stronger stimulus to CRP production. Some of the differences in the inflammatory processes of ulcerative colitis and Crohn's disease may reflect differences in the amount of IL-1beta and IL-6 generated from macrophages and monocytes.
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PMID:Interrelations between interleukin-6, interleukin-1 beta, plasma C-reactive protein values, and in vitro C-reactive protein generation in patients with inflammatory bowel disease. 820 May 75

Chronic inflammation in inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) may be attributed partly to increased secretion of inflammatory cytokines. The aim of this study was to investigate simultaneously the spontaneous release patterns of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1 beta), and interleukin-6 (IL-6) by organ cultures of inflamed mucosa from IBD patients. Organ cultures of involved IBD mucosa spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6 compared to normal mucosa. The patterns of cytokine release between Crohn's disease and ulcerative colitis organ cultures were not significantly different. Increased inflammatory cytokine production by lamina propria mononuclear cells (LPMCs) and mucosa treated with EDTA suggests that these cytokines originate mainly from LPMCs. These results confirm the role of inflammatory cytokines in IBD and shed a new light on the role of TNF-alpha in IBD.
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PMID:Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn's disease. 873 57

Previous studies have demonstrated elevated serum levels of interleukin-6 (IL-6) and the soluble interleukin-2 receptor (IL-2R, CD25) in individuals with inflammatory bowel disease (IBD). The aim of our study was to compare serum IL-6 and IL-2R levels to see if one marker better distinguished IBD from other intestinal disorders or better reflected disease activity. Blood samples were obtained from 41 pediatric patients with Crohn's disease, 22 with ulcerative colitis, 19 with other gastrointestinal inflammatory disorders, and 13 with functional abdominal pain. Disease activity and disease location were determined for patients with Crohn's disease and ulcerative colitis. Serum levels of IL-6 and IL-2R were determined by using an enzyme-linked immunosorbent assay. Mean serum levels of IL-6 were significantly elevated (p < 0.05) in patients with Crohn's disease when compared with individuals with ulcerative colitis, other gastrointestinal inflammatory disorders, or functional abdominal pain. By comparison, there was no significant difference in mean serum levels of IL-2R in individuals with Crohn's disease compared with these other groups. Patients with moderate/severe Crohn's disease had elevated mean serum levels of IL-6 and IL-2R when compared with those with mild and inactive disease (p < 0.05); however, neither marker distinguished between inactive and mild disease. IL-6 correlated better with the erythrocyte sedimentation rate (ESR; r = 0.57, p < 0.001) than did IL-2R (r = 0.28, p < 0.01). Our results suggest that elevated IL-6 levels a.e more likely to be seen in patients with Crohn's disease. Although IL-6 may be a better marker for Crohn's disease and active disease than IL-2R, it does not appear to offer any advantage over the ESR.
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PMID:Elevation of serum interleukin-6 but not serum-soluble interleukin-2 receptor in children with Crohn's disease. 885 84

Microcirculatory disturbances of the colon may contribute to the pathogenesis of inflammatory bowel disease. The aim of the study was to investigate the alterations of rectal blood perfusion in experimental colitis with reference to nitric oxide and heparin treatment. The study was carried out on 36 rats, divided into six groups: group I, control; group II, control + NG-nitro-L-arginine (L-NNA); group III, colitis without treatment; group IV, colitis + L-arginine; group V, colitis + L-NNA; group VI, colitis + heparin treatment. Experimental colitis was induced by 4% acetic acid enema, and 48 h after the enema, besides the measurement of rectal capillary blood flow by means of laser Doppler flowmetry, the serum interleukin-6 (IL-6) level and histopathological alterations within the rectal mucosa were examined. Experimental colitis resulted in a drop in rectal wall perfusion. L-Arginine and heparin treatment improved the microcirculatory values. The highest IL-6 level and the most advanced histopathological alterations were observed in the rats treated with L-NNA. L-Arginine treatment had no influence on IL-6 concentration, however it aggravated the inflammatory changes within the rectal mucosa. Heparin administration reduced the IL-6 values and also had a positive impact on the microscopic alterations within the rectal wall. It is concluded that heparin treatment has a beneficial effect on the microcirculatory disturbances and inflammatory changes observed in experimental colitis. The inhibition of nitric oxide-synthase aggravated the course of experimental colitis. L-Arginine administration improves the rectal blood flow but aggravates the histopathological alterations within the rectal wall.
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PMID:Is nitric oxide and heparin treatment justified in inflammatory bowel disease? An experimental study. 898 63

The normal intestinal immune system is under a balance in which proinflammatory and anti-inflammatory cells and molecules are carefully regulated to promote a normal host mucosal defense capability without destruction of intestinal tissue. Once this careful regulatory balance is disturbed, nonspecific stimulation and activation can lead to increased amounts of potent destructive immunologica and inflammatory molecules being produced and released. The concept of balance and regulation of normal mucosal immune and inflammatory events is indicative of how close the intestine is to developing severe inflammation. The normal intestinal mucosal immune system is constantly stimulated by lumenal contents and bacteria. The stimulatory molecules present in the intestinal lumen that activate and induce subsequent mucosal immunologic and inflammatory events include bacterial cell wall products, such as peptidoglycans and lipopolysaccharides, as well as other chemotactic and toxic bacterial products that are produced by the many different types of bacteria within the gastrointestinal tract. These highly stimulatory bacterial cell wall products are capable of activating macrophages and T lymphocytes to release potent proinflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). IL-1, IL-6, and TNF-alpha increase the presence of human leukocyte antigen (HLA) class II antigen-presenting molecules on the surfaces of epithelial cells, endothelial cells, macrophages, and B cells, thus increasing their ability to present lumenal antigens and bacterial products. The proinflammatory cytokines IL-1 and TNF-alpha also increase the ability of epithelial cells, endothelial cells, macrophages, and fibroblasts to secrete potent chemotactic cytokines, such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), which serve to increase the movement of macrophages and granulocytes from the circulation into the inflamed mucosa. Thus, through lumenal exposure to potent, nonspecific stimulatory bacterial products, the state of activation of the intestinal immune system and mucosal inflammatory pathways are markedly up-regulated. This raises the question of whether there is a deficiency in effective down-regulation through the absence of normally suppressive cytokines such as interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), interleukin-4 (IL-4), and IL-1 receptor antagonist. Normally, the turning off of the active and destructive immunologic and inflammatory events should occur following the resolution of a bacterial or viral infection that has been appropriately defended against and controlled by the mucosal immune system. In inflammatory bowel disease (IBD), however, the down-regulatory events and processes that should turn off the immunologic and inflammatory protective processes, once the pathogenic agent has been cleared, appear to be deficient or only partially effective. We may find that we ultimately are dealing with disease processes that have more than one genetic or cellular basis. The improved understanding of the immunopathophysiology of IBD will allow exploration of novel immunologic and genetic approaches, such as gene replacement therapy, administration of a suppressor cytokine or an altered cell surface antigen, the administration of humanized monoclonal antibodies directed against proinflammatory cytokines, or the development of newer strategies against fundamental cell biologic mechanisms such as adhesion molecules.
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PMID:Alterations of the mucosal immune system in inflammatory bowel disease. 902 61

Patients with active inflammatory bowel disease are often reported to be in negative nitrogen balance. Therefore, we examined basal and amino acid stimulated urea synthesis in 11 patients with active inflammatory bowel disease and in 10 patients with non-active disease. A primed continuous infusion of an amino acid mixture was given from t = 1 h to t = 5 h; during the first and the last two hours no amino acid infusion was given. Urea nitrogen synthesis rate was quantified independently of changes in blood amino acid concentration by means of the functional hepatic nitrogen clearance, i.e. the linear slope of the regression of urea nitrogen synthesis rate on blood amino acid concentration. Basal and amino acid stimulated urea nitrogen synthesis rate as well as functional hepatic nitrogen clearance were elevated twofold in the patients with active disease. No differences between the two groups were observed as regards basal or stimulated plasma glucagon, cortisol, catecholamines and serum levels of interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6. The results show that liver function related to conversion of amino-nitrogen to urea is increased and may contribute to the less efficient nitrogen economy in patients with active inflammatory bowel disease.
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PMID:[Increased urea synthesis in patients with active inflammatory bowel disease]. 941 71

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

Many nutritional issues are important in the care of children and adolescents with inflammatory bowel disease. No specific dietary toxin or antigen has been identified to have an etiologic role in either ulcerative colitis or Crohn's disease. A possible modulating effect of omega-3 polyunsaturated fatty acids on intestinal inflammation is being investigated. Most prevalent among the nutritional consequences of inflammatory bowel disease is weight loss, for which inadequate caloric intake is primarily responsible. Impairment of linear growth and associated delay in pubertal development commonly complicate childhood Crohn's disease. The two major etiologic factors are chronic undernutrition and direct effects of inflammatory mediators secreted from the inflamed gut. Recent studies have incriminated interleukin-6. Treatment of intestinal inflammation and provision of adequate nutrition are of paramount importance in preventing or remedying growth impairment. Exclusive enteral nutrition using formulated food is efficacious primary therapy of active Crohn's disease, although the mode of action is poorly understood.
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PMID:Inflammatory bowel disease. 978 63


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