Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009324 (ulcerative colitis)
 17,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whatever initiates inflammation, the final message mediating cellular invasion is chemical. This consideration allows rational development of anti-inflammatory treatments. Two main classes of chemotactic mediator are recognised. Water-soluble peptides, e.g. cytokines derived from macrophages and other cells, play an important integrating part in the early recruitment of neutrophils and mononuclear cells, and in the amplification of immune responses. Lipid-soluble mediators, of which leukotriene B4 is the most highly chemotactic for neutrophils, are important in secondary amplification. In inflammatory bowel disease, we have shown evidence of increased synthesis of cytokines interleukin 1, 6 and 8. These are associated with activation of circulating monocytes in active Crohn's disease, of lamina propria macrophages in relapse of both ulcerative colitis and Crohn's disease, and development of adhesion molecules on vascular endothelium. Our studies show that interleukin 6 is selectively increased in Crohn's disease, whilst preliminary findings suggest that enhanced synthesis of interleukin 8 is particularly characteristic of ulcerative colitis. Patterns of cytokine synthesis may, therefore, be of diagnostic value. They also offer the potential for therapeutic strategies since cytokine antagonists are becoming available. We have also demonstrated increased synthesis of leukotrienes in active inflammatory bowel disease. Since leukotriene B4 is quantitatively the main chemotactic signal in the mucosa in inflammatory bowel disease during relapse, we investigated the therapeutic effect of suppressing leukotriene B4 synthesis by treating patients with fish oil (as Hi-EPA), giving 4.5 g daily of eicosapentaenoic acid. This competes for the 5-lipoxygenase enzymes, inhibiting leukotriene B4 and promoting synthesis of the less chemotactic product, LTB5.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic interventions in gastrointestinal disease based on an understanding of inflammatory mediators. 135 43

Epithelia from several sites exhibit inducible secretion of interleukin 8 (IL-8). This study aimed to characterise secretion of IL-8 by colonic epithelial cells in vitro. Colonic crypt cells were isolated enzymatically from resected colon and the IL-8 content of culture supernates was measured by ELISA. The rate of secretion of IL-8 accelerated and levels of IL-8 transcripts increased appreciably during culture. Exposure to tumour necrosis factor alpha (TNF alpha) failed to increase secretion further. Secretion was not induced by the enzymatic digestion or by serum used in the culture medium but was significantly inhibited by butyrate, by a mean of 23%. Control experiments indicated that colonic crypt cells were the likely source. The secretion of IL-8 over 24 hours by cells from uninflamed mucosa of patients with ulcerative colitis or Crohn's disease was more than twofold that from normal cells, while that from cancer bearing colons was normal. TNF alpha (10 mM) significantly suppressed IL-8 secretion only in the ulcerative colitis group and the change was different to those in the normal (p = 0.007) and Crohn's disease groups (p = 0.012). Cells from inflamed areas secreted more IL-8 than those from autologous uninflamed areas (p = 0.009) but responses to modulating factors were no different. The induction of IL-8 secretion by colonic crypt cells in vitro is probably a response to injury associated with isolation and culture. It is suppressed by butyrate and increased in inflammatory bowel disease independently of the presence of mucosal inflammation. Whether epithelial derived IL-8 plays a part in the pathogenesis of inflammatory bowel disease is not yet clear.
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PMID:Interleukin 8 secretion by colonic crypt cells in vitro: response to injury suppressed by butyrate and enhanced in inflammatory bowel disease. 748 42

To clarify the mechanisms of action of immunoglobulin (IgG) in intravenous immunoglobulin therapy for the ulcerative colitis (UC) patients, we studied the therapeutic effect of IgG on experimental rat colitis induced by dextran sulfate sodium and on the production of inflammatory cytokines such as TNF alpha, IL-1 alpha and IL-8. The administration of rat IgG demonstrated to suppress the development of blood stool and the induction of the ulcerative lesion in large intestine. The levels of TNF alpha, IL-1 alpha and IL-8 were increased in blood and mucosa of the large intestine in this model. Rat IgG showed a tendency to decrease the levels of the cytokines in colonic mucosa. This result seems to provide a piece of explanation of how massive administration of IgG shows an improvement in the ulcerative lesion of UC patients.
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PMID:[Effect of gamma-immunoglobulin in experimental colitis induced by dextran sulfate]. 796 29

IL-8 is generating increasing interest as a powerful neutrophil chemoattractant and activator. To elucidate the mechanisms of neutrophil infiltration in inflammatory bowel disease, we examined 33 patients with ulcerative colitis (UC), 18 with Crohn's disease (CD), eight with some other type of colitis, and 18 normal control subjects for measurement of IL-8 in homogenates of colonic biopsy specimens. The affected colonic mucosa was found to contain significantly more IL-8 in patients with active inflammatory bowel disease than in patients with inactive disease (UC, P < 0.001; CD, P < 0.001), in patients with other types of colitis (UC, P < 0.05; CD, P < 0.01), or in normal control subjects (UC, P < 0.001; CD, P < 0.001). Colonic IL-8 levels correlated significantly with the macroscopic grade of local inflammation, especially in patients with UC (P < 0.001). Colonic IL-8 levels also correlated well with the neutrophil numbers in mucosal tissue (UC, r = 0.950, P < 0.001; CD, r = 0.940, P < 0.001), and with colonic IL-1 beta (r = 0.911, P < 0.001) and tumour necrosis factor-alpha (TNF-alpha) levels (r = 0.604, P < 0.001) in patients with these two conditions. These data suggest a potential role for IL-8 and its regulatory cytokines IL-1 and TNF-alpha in mediating neutrophil infiltration of the gut wall in inflammatory bowel disease.
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PMID:IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease. 800 12

Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction.
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PMID:Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation. 817 48

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

To clarify the mechanism of action of immunoglobulin (IgG) in intravenous immunoglobulin therapy for ulcerative colitis (UC) patients, we studied the effect of IgG on the dynamics of immunocompetent cells in the colonic mucosa of experimental colitis induced by dextran sulfate sodium (DSS) in rats. The administration of the same species' IgG suppressed the mucosal infiltration of immunocompetent cells (activated T cells, macrophages and neutrophils), although the different species' IgG didn't. We have already shown that the same species' IgG, suppressed the production of inflammatory cytokines (TNF alpha, IL-1 alpha and IL-8) in the colonic mucosa of experimental colitis induced by DSS. In the present report, we demonstrated the different species' IgG, as well as same species' IgG, suppressed the production of inflammatory cytokines (TNF alpha and IL-1 alpha) from lamina propria mononuclear cells of rat large intestine in vitro. Therefore, it was considered that the suppression of cytokine production was a consequence of the decreased immunocompetent cells in colitis mucosa. Furthermore, we demonstrated that the DSS-treated antigen presenting cells (APCs) activated antigen-specific T cells as a possible mechanism underlying the colitis induced by DSS and the same species' IgG inhibited this activation of T cells.
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PMID:[Immunological effect of immunoglobulin on experimental colitis induced by dextran sulfate]. 855 75

We investigated the production of proinflammatory cytokines (IL-1 beta, IL-6, IL-8, and TNF-alpha) and immunoregulatory cytokines (IL-2, IFN-gamma, and IL-10) in the colonic mucosa of patients with active ulcerative colitis (UC), inactive UC, and non-inflammatory bowel disease (IBD) colitis by organ culture. The production of proinflammatory cytokines was significantly increased in all the studied groups compared with controls. In active UC, levels of these cytokines, except for IL-1 beta, were markedly increased compared with non-IBD colitis, and the levels were positively correlated with the degree of inflammation. Patients with non-refractory active UC receiving steroids showed levels of IL-1 beta and TNF-beta production similar to those in controls. IL-10 production was also significantly increased in all the studied groups, the value of being the highest in active UC. In contrast, IL-2- and IFN-gamma production was significantly decreased in both active and inactive UC compared with controls, and the values in active UC were inversely correlated with the degree of inflammation. In non-IBD colitis, decreased IL-2 production was observed, but IFN-gamma production did not differ from that in controls. In an experimental study, each of the proinflammatory cytokines was injected into the colonic mucosa of rats. All of these proinflammatory cytokines, except for IL-1 beta induced colonic mucosal damage that showed some histologic features similar to those of UC. These results suggest that the increased production of proinflammatory cytokines, particularly of IL-6 and IL-8, and the decreased production of IL-2- and IFN-gamma, probably downregulated by the enhanced production of IL-10, play an important role in the pathogenesis of UC.
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PMID:The role of proinflammatory and immunoregulatory cytokines in the pathogenesis of ulcerative colitis. 856 92

We investigated the lymphocyte-activation antigens and the expression of cytokine genes in the mucosa of ulcerative colitis (UC). Fresh colonic mucosal biopsy specimens from patients with UC and controls were fixed for the immunohistochemical study of CD4, HLA-DR, and CD25, and other specimens were prepared for the RNA analysis of cytokines. Gene expression was evaluated by the reverse transcription-polymerase chain reaction, and the radioactivity of dot-blotted amplified cDNA was standardized by co-amplified beta-actin cDNA. The inflamed mucosa of active UC showed increased CD4+DR+ and CD25+ cells in comparison with control subjects. Active UC showed significantly increased mRNA expression of IL-1 beta, IL-2R alpha, IL-6, IL-8, and TNF alpha compared with the controls. We found no significant difference in the mRNA expression for IL-2, IL-4, IL-10, and IFN-gamma between active UC and controls. Increased CD4+DR+ and CD25+ cells in active UC mucosa indicate mucosal CD4(+) T cell activation in the lamina propria, but we did not clarify Th1 or Th2 specific T cell activation from our study of cytokine mRNA expression. The increased mRNA expression for IL-1 beta, IL-6, and TNF alpha in the mucosal lesions of UC indicates that these inflammatory cytokines may play important roles in the pathogenesis of UC.
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PMID:Study of cytokines in ulcerative colitis. 856 93

To test whether there is a difference in the expression of interleukin 8 (IL8) between Crohn's disease and ulcerative colitis and to determine the main site of its synthesis this study analysed IL8 in mucosal biopsy specimens of patients with Crohn's disease and ulcerative colitis by enzyme linked immunosorbent assay (ELISA) and by in situ hybridisation. IL8 was measured by ELISA in 38 normal control patients, eight inflammatory control patients, 55 Crohn's disease biopsy specimens (26 patients), and 67 ulcerative colitis biopsy specimens (35 patients). IL8 mRNA was determined in samples by in situ hybridisation using a specific IL8 RNA probe. IL8 protein was significantly increased in macroscopically inflamed specimens of Crohn's disease (median 118 pg/specimen, p < 0.0001), ulcerative colitis (median 140 pg/specimen, p < 0.001), and inflammatory controls (median 30 pg/specimen, p = 0.010) compared with normal controls (median 4 pg/specimen). IL8 was also increased in uninflamed specimens of Crohn's disease (median 46 pg/specimen, p < 0.001) but not of ulcerative colitis patients (median 9 pg/specimen, p = 0.3). IL8 protein in the mucosa correlated significantly with macroscopic inflammation in Crohn's disease (r = 0.47, p < 0.001) and in ulcerative colitis (r = 0.60, p < 0.001). IL8 mRNA was detected by in situ hybridisation in 31 of 55 biopsy specimens (56%) of Crohn's disease patients, in 38 of 67 specimens of ulcerative colitis patients (57%), in five of eight inflammatory controls (63%) and in five of 38 normal controls (13%). Mucosal IL8 mRNA expression correlated with mucosal IL8 protein (r = 0.46, p < 0.001). IL8 mRNA was only detected in inflammatory cells of the interstitium but not in mucosal epithelial cells. IL8 is produced mainly in the lamina propria of the colon in inflammatory bowel disease and correlates with mucosal inflammation.
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PMID:Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease. 880 Dec


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