Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mucosal immune system consists of a number of compartments that are populated with a different assortment of cells and serve different functions. The cytokines produced by the cells in each of these compartments are currently being defined. This is best understood in relation to B cells, whose proliferation and maturation is guided by a sequence of cytokines. PP are inductive sites that preferentially stimulate IgA production. At least in part, this preference seems to be due to the T cells located in PP, which have been shown to stimulate switching to IgA production by cognate interactions and production of TGF-beta. Postswitch B cells expressing surface IgA respond to IL-5, a cytokine produced by T cells in GALT. Terminal differentiation to IgA-producing plasma cells in the lamina propria may be driven by IL-6, which can be produced by a variety of cells in the lamina propria and by epithelial cells. T cells in the lamina propria have an assortment of surface markers consistent with both activation and memory and appear to produce a variety of cytokines in the local environment that presumably act in normal host defense. IEL consist mainly of CD8+ T cells. They have been shown to produce IFN-gamma and, very likely, other cytokines that presumably act in a paracrine fashion on local enterocytes. How these cells and cytokines are perturbed during intestinal inflammation is currently being defined. A certain assortment of cytokines are greatly increased in IBD. This assortment, including IL-1, IL-6, and IL-8, is elevated in a wide variety of chronic inflammatory states in other tissues as well. A critical requirement for cytokines to exert their effects is the expression of specific receptors on target cells. Virtually nothing is known about this aspect of mucosal immunity, but receptor expression on mucosal cells must be defined before we will be able to understand the complex interactions among lymphoid cells, the cytokines they produce, and the local stromal and epithelial cells.
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PMID:Cells and cytokines in mucosal immunity and inflammation. 151 47

Continued delineation of the major factors that lead to intestinal inflammation will provide critical insights into many of the pathophysiologic events leading to tissue destruction in IBD. The exploration of exciting and important new areas, such as the role of adhesion molecules, proinflammatory cytokines, and the activation of lymphocytes and phagocytes, will contribute significantly to a better understanding of the mechanisms that sustain the intestinal inflammatory process. Determining the mechanisms of amplification and perpetuation of intestinal inflammation as well as learning more about the natural suppression of intestinal inflammation by the normal cellular and cytokine networks of the mucosal immune system will open exciting new therapeutic approaches. It is encouraging to see realistic and testable working models emerge from the combined efforts of many committed investigators who have been engaged in studying the role of the mucosal immune system in the pathophysiology of IBD. A great deal more remains to be learned in this rapidly advancing area, and we can look forward with confidence to continued advances in the study of IBD.
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PMID:The role of the mucosal immune system in inflammatory bowel disease. 151 51

We have described a murine model of IBD that was induced in C.B-17 scid mice by transfer of the CD45RBhi subpopulation of CD4+ T cells from normal BALB/c mice and could be prevented by cotransfer of the CD45RBlo CD4+ T cell subset. Here we have dissected the mechanism of pathogenesis of IBD in this model and used this information for rational immunotherapy of the disease. CD4+ cells from diseased mice displayed a highly polarized Th1 pattern of cytokine synthesis upon polyclonal stimulation in vitro. The administration of anti-IFN gamma MAb to mice soon after T cell transfer prevented development of colitis for up to 12 weeks. Continual neutralization of TNF with anti-TNF MAbs reduced the incidence of severe disease; however, neutralization of TNF during only the first 3-4 weeks had no effect. Severe colitis was completely abrogated in mice treated systemically with rIL-10, but not with rIL-4.
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PMID:Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. 760 Feb 84

IBD is characterized by increased serum concentrations of different cytokines. IL-10 inhibits the production of proinflammatory cytokines such as IL-1, tumour necrosis factor-alpha (TNF-a), interferon-gamma (IFN-gamma) and IL-6 through inhibitory action on Th1 cells and macrophages, and it is thought to be a suppressor type cytokine. In the present study we determined serum concentrations of IL-10 in patients with ulcerative colitis (UC) and Crohn's disease (CD). We measured human IL-10 by our own newly established ELISA system using PharMingen antibodies. Serum antibodies were assessed in 44 patients with UC, 40 patients with CD, and in 30 healthy controls. Human IL-10 serum levels were significantly increased in patients with active UC (144 +/- 34 pg/ml (mean +/- s.e.m.), P < 0.001) and in active CD (132 +/- 32 pg/ml, P < 0.001) compared with healthy controls (44 +/- 9.5 pg/ml). Only patients with active CD and active UC presented with significantly increased IL-10 serum levels, while patients with inactive disease did not show any significant increase. There was no statistically significant difference between IL-10 serum levels in patients with CD or UC. Compared with clinical disease activity indices there was a significant correlation between IL-10 serum concentration and CDAI in patients with CD (r = 0.45, P < 0.01) and CAI in UC patients (r = 0.39, P < 0.05). Comparing IL-10 serum levels with serum concentrations of other proinflammatory cytokines there was a significant correlation to serum levels of sIL-2R (r = 0.417, P < 0.05) and IL-6 (r = 0.387, P < 0.05) in patients with CD. Serum cytokine levels in patients with UC did not show any significant correlation to IL-10 serum concentration. IL-10 is elevated in serum of patients with active CD and UC, suggesting that IL-10 acts as a naturally occurring damper in the acute inflammatory process of IBD.
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PMID:Circulating antiinflammatory cytokine IL-10 in patients with inflammatory bowel disease (IBD). 777 55

1. Tumour necrosis factor is a proinflammatory macrophage-derived polypeptide cytokine. Its participation in disease processes has been usually inferred from data obtained from experiments in vitro or from measurements of its plasma circulating levels. To investigate its role in chronic ulcerative colitis, we have quantified in vivo the steady-state release of tumour necrosis factor into the colonic lumen. 2. We studied 19 patients with untreated active ulcerative colitis and seven patients with irritable bowel syndrome as controls. A group of seven patients with active ulcerative colitis were studied before and after 4 weeks on treatment with oral 5-aminosalicylic acid. By means of an intracolonic double-lumen perfusion tube, an isotonic solution was continuously infused 50 cm from the anal verge at a rate of 5 ml/min, and was recovered 30 cm distally by siphonage. Effluents were assayed for tumour necrosis factor by a specific e.l.i.s.a. and for prostaglandin E2 and leukotriene B4 by specific r.i.a.s. 3. The intracolonic release of tumour necrosis factor was undetectable in patients with irritable bowel syndrome, whereas measurable release occurred in 15 out of 19 patients with active ulcerative colitis (P < 0.01). Prostaglandin E2 and leukotriene B4 release were also increased in active ulcerative colitis by comparison with irritable bowel syndrome (P < 0.01). Five out of seven patients with colitis improved with 5-aminosalicylic acid treatment, and tumour necrosis factor release became undetectable or decreased markedly (P < 0.05 compared with before treatment). However, tumour necrosis factor release remained high in the non-responder patients. 4. These findings indicate that intracolonic immunoreactive tumour necrosis factor release is enhanced in active chronic ulcerative colitis, becoming undetectable when mucosal lesions are healed. These results suggest that the luminal release of tumour necrosis factor may serve as an objective index of inflammatory activity in patients with chronic ulcerative colitis.
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PMID:Intraluminal colonic release of immunoreactive tumour necrosis factor in chronic ulcerative colitis. 783 99

Management strategies in Crohn's disease and ulcerative colitis should be based on up-to-date information on disease distribution, extent, activity and complications. A system of structured analysis is suggested, with separate consideration of destructive ulceration, inflammatory activity and other factors. Direct investigation of gut immunity by using whole gut lavage fluid (WGLF) is a valuable new technique of clinical investigation in IBD and related disorders. Recent studies have shown that the concentrations of plasma-derived proteins in WGLF provide objective measures of disease activity; and that this activity is a separate phenomenon from destructive ulceration and fibrosis. Neutrophils in the lumen can be in- investigated by cytology, or by assay of neutrophil elastase in WGLF. Cytokines and other immuno-regulatory mediators can also be detected. These new techniques can provide a description of intestinal immunity and inflammation, based on a non-invasive test of 2-4 h duration. Work in progress shows that patients who respond clinically to elemental diet treatment have unusually high concentrations of soluble IL2 receptor in WGLF; cytokine profiles may facilitate the selection of patients suitable for other new treatment modalities.
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PMID:Analysis of disease distribution, activity and complications in the patient with inflammatory bowel disease. 797 42

Hallmarks of IGF-I action include synergy with other hormones and growth factors and the ability to stimulate proliferation or differentiated cell function dependent on physiological or pathophysiologial context. A complete understanding of IGF action in IBD will require analyses of mechanisms of IGF interaction with other growth factors, hormones and cytokines. GH and IGF-I may be administered to children over prolonged periods to correct growth disorders. The definition of the benefits and problems of GH/IGF-I therapy in IBD needs to distinguish between long-term and short-term effects. Short-term administration of GH and IGF-I to animal models of IBD such as the PG-PS and TNBS models, which share features of Crohn's disease (Sartor, 1992), and a recently developed murine model of ulcerative colitis induced by ingestion of dextran sulphate (Okayasu et al, 1990; Sartor, 1992; Cooper et al, 1993) could address the beneficial or detrimental consequences of short-term GH/IGF-I therapy. Adaptation of the PG-PS, TNBS and dextran sulphate models of inflammation to available transgenic mouse lines that over-express GH and IGF-I (Behringer et al, 1990; Ulshen et al, 1993), especially if over-expression is inducible, could help to define the potential benefits and problems of long-term GH/IGF-I therapy or the effects of GH/IGF-I on immune cell function and cytokine production during intestinal inflammation. It will be useful to study intestinal inflammation and complication in animal models of GH or IGF-I deficiency. In this regard, mice with targeted ablation of the IGF-I gene could be useful (Liu et al, 1993) although neonatal mortality in these models currently poses problems for in vivo studies. Development of mesenchymal cell lines from such animals could, however, provide a useful in vitro system to study the role of IGF-I in altered cell function in response to pro-inflammatory cytokines.
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PMID:Insulin-like growth factors and inflammatory bowel disease. 873 2

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

If one reviews the literature with zeal, it is increasingly apparent that few organs escape recruitment when IBD is chronic or progressive. Insights into mucosal pathophysiology have helped with understanding the more frequent extraintestinal manifestations, but the mechanisms attendant to the development of less common events (e.g. acute pancreatitis, concurrent gluten sensitive enteropathy, or active pulmonary disease) remain either poorly studied or obscure. It is particularly interesting, however, to read reports of abnormal pulmonary function, generally of the obstructive type, correlated to measurements of abnormal intestinal permeability in patients with either active pulmonary sarcoid or pulmonary involvement in Crohn's disease. It has been further speculated that similarities in the mucosal immune system of the lung and intestine are responsible for evidence of bronchial hyperreactivity in patients with active IBD. Finally, it is important to recognize that extensions of the inflammatory process are not restricted to the development of organ-based events but may be responsible for some of the most frequent systemic abnormalities detected in IBD patients. It is now also well confirmed that the cytokine environment in IBD can support activated coagulation and, in some clinical situations, overt vascular thrombosis. The cerebrovascular complications of IBD are well recognized and range from peripheral venous thrombosis to central stroke syndromes and pseudotumor cerebri. Reports of focal white matter lesions in the brains of patients with IBD or an increased incidence of polyneuropathy may be other clinical examples of regional microvascular clotting. Microvascular injury appears to be more ubiquitously present, with reports ranging from a speculated primary causative role (e.g., granulomatous vasculitis in the mesenteric circulation) to the utility of nailbed vasospasm, in Crohn's disease, as a clinical marker for disease activity. It is also reported that IL-6 suppression of erythropoietin production is a major feature of the chronic anemia seen in active IBD. Moreover, the capacity of peripheral monocytes from active IBD patients to secrete TNF and IL-8 is reported predictive for the degree of therapeutic response from recombinant erythropoietin. These collected observations constitute another excellent example of the symmetry between basic science and clinical utility. It is from the context of applied basic science that many future therapies will arise. Empiricism will lose much of its appeal as clinical observations will be increasingly translated into cellular language. Already in animal models, elemental diets diminish IL-6-related acute inflammatory injury, and reductions in dietary lipid alter the antigenicity of bacteria. Provocatively, in humans, unconfirmed reports have even associated diet therapy with the resolution of uveitis and pyoderma gangrenosum. It is likely that efforts will also be made to induce oral tolerance if specific triggering proteins are discovered or to alter bowel flora if such an arcane area of investigation becomes resurgent.
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PMID:Extraintestinal considerations in inflammatory bowel disease. 880 40

Several theories have already been postulated in connection with the pathogenesis of inflammatory bowel diseases, yet none of them has been approved. Recently increasing attention has been payed to different cytokines, playing central role in the development of inflammatory processes. In the intestinal mucosa of patients suffering from inflammatory bowel diseases increasing amounts of interleukin-1 (IL-1), tumor necrosis factor (TNF) and platelet activating factor (PAF) could be measured. On the other hand, antiinflammatory cytokines seem to be ineffective, or being present in insufficient amount (IL-4 and IL-10 respectively). It is therefore probable, that altered ratios of cytokines, or pathologic regulation of their production lead to progression of inflammation in IBD. Influence of cytokine production may open new therapeutic approach, e.g. IL-10 enema proved to be effective in the treatment of some cases of steroid-resistant ulcerative colitis, while intravenous administration was useful in Crohn's disease. A brief, comprehensive review of our present knowledge about cytokines in IBD is given.
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PMID:[The role and significance of the most important known cytokines in inflammatory bowel diseases]. 963 23


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