Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Altered peripheral neutrophil function is a feature of IBD that may contribute to the chronicity and extragastrointestinal manifestations of this disease, but clinical evidence for such alterations is confounded by variations in patient characteristics, disease onset, and use of therapeutics that can influence neutrophil function. The use of a rat model of colitis has permitted us to characterize, in a controlled manner, the causal relationship between colitis and altered peripheral neutrophil function. At various times after induction of colitis with trinitrobenzene sulfonic acid (TNBS), peripheral neutrophils were isolated and assays of phagocytosis, chemotaxis, leukotriene B4 (LTB4) synthesis, and superoxide production were performed using a variety of stimuli. Circulating neutrophil numbers increased about fourfold within 12 hr of TNBS administration and returned to normal levels over the following two weeks. LTB4 synthesis in response to calcium ionophore decreased at 12 hr after induction of colitis, then returned to control levels. The chemotactic responses of peripheral neutrophils to LTB4 and FMLP in vitro and to LTB4 and IL-8 in vivo were profoundly suppressed through the two-week study period. Phagocytosis of nitroblue tetrazolium was significantly enhanced (ca. threefold) at 12 hr after induction of colitis and remained elevated throughout the study period. Superoxide production was also significantly elevated in the early phase of colitis (by ca. fourfold), but was not different from control levels at seven and 14 days. These results demonstrate that colonic inflammation profoundly influences peripheral blood neutrophil function, although the direction and magnitude of the alteration varied among the various functions assessed. The prolonged depression of chemotactic activity may represent a physiological reaction to limit the inflammatory response.
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PMID:Alterations in rat peripheral blood neutrophil function as a consequence of colitis. 782 Nov 10

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

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

Fibrosing colonopathy is a recently described complication of cystic fibrosis, of unknown aetiology but possibly related to treatment with high-dose pancreatic enzyme supplements. We have used a whole gut perfusion technique to study subclinical gut inflammation in cystic fibrosis patients; concentrations of haemoglobin, IgG, albumin, alpha-1-antitrypsin, granulocyte elastase, IL1 beta, and IL8 were measured in whole gut lavage fluid: 23 tests were performed in 17 children with cystic fibrosis (20 elective tests, three lavages to treat distal intestinal obstruction syndrome (DIOS)). None has had fibrosing or haemorrhagic colitis. There were 12 tests in control children with constipation or precolonoscopy. Moderately abnormal results were obtained for many of the parameters studied, in specimens from all the cystic fibrosis children; however there were no significant differences between tests on high-dose and low-dose enzyme supplements of the same brand in the five children who had duplicate tests performed electively. The lavage fluid specimens from two cystic fibrosis children were strikingly abnormal in all tests apart from haemoglobin and alpha-1-antitrypsin. These were two of the three children with DIOS, and were also the only cases in the series taking Nutrizym 22. These data suggest that the majority of cystic fibrosis children, including those on high-dose enzyme supplements, do not have clinically significant colitis, but that there is subclinical mucosal inflammation in a minority (two of 17 in this series), for which DIOS and/or Nutrizym 22 treatment may be risk factors. Alternatively, inflammation and dysmotility in the proximal colon may be directly produced by a drug or other agent, producing a clinical syndrome indistinguishable from DIOS. Tests for indices of inflammation in gut lavage fluid offer a new approach to the detection and measurement of iatrogenic intestinal and colonic injury.
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PMID:Direct assessment of gastrointestinal inflammation and mucosal immunity in children with cystic fibrosis. 886 80

Controlled clinical trials have shown that several immunosuppressive drugs are efficacious in patients with inflammatory bowel disease. These drugs each have multiple effects on the immune system and the exact mechanism of their beneficial effect in inflammatory bowel disease is unknown. None of these agents directly inhibits the 'inflammatory cytokines' such as IL-1 beta, IL-6, IL-8, or TNF-alpha. However, they can all inhibit generation of leukocyte precursors in the bone marrow, that is, the cells that produce such cytokines. The effects of current agents on T-cell subsets and their associated cytokines remains unclear. Based on insights from novel mouse models of chronic colitis, the goal of 'immunotherapy' going into the next decade should be either to inhibit specifically the effector T cells mediating disease or to enhance the regulatory T cells that inhibit such effector cells or, ideally, to do both. Therapy meeting this goal, which will need to based on a more thorough understanding of the immunopathogenesis of inflammatory bowel disease, should allow a more specific or 'surgical' approach to immunotherapy and simultaneously reduce its risks and adverse effects.
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PMID:The effects of immunosuppressive agents on cytokines. 889 8

Cytokines play a central role in the modulation of the intestinal immune system. They are produced by lymphocytes (especially T cells of the Th1 and Th2 phenotypes), monocytes, intestinal macrophages, granulocytes, epithelial cells, endothelial cells, and fibroblasts. They have proinflammatory functions [interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6, IL-8, IL-12] or antiinflammatory functions [interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, IL-11, transforming growth factor beta (TGF beta)]. Mucosal and systemic concentrations of many pro- and antiinflammatory cytokines are elevated in inflammatory bowel disease (IBD). An imbalance between proinflammatory and antiinflammatory cytokines was found for the IL-1/IL-1ra ratio in the inflamed mucosa of patients with Crohn's disease, ulcerative colitis, diverticulitis, and infectious colitis. Furthermore, the inhibition of proinflammatory cytokines and the supplementations with antiinflammatory cytokines reduced inflammation in animal models, such as the dextran sulfate colitis (DSS) model, the trinitrobenzene sulfonic acid (TNBS) model, or the genetically engineered model of IL-10 knockout mice. Based on these findings a rationale for cytokine treatment was defined. The first clinical trials using neutralizing monoclonal antibodies against TNF alpha (cA2) or the antiinflammatory cytokine IL-10 have shown promising results. However, many questions must be answered before cytokines can be considered standard therapy for IBD.
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PMID:Cytokines in inflammatory bowel disease. 952 21

Proinflammatory cytokines are believed to be involved in the pathogenesis of ulcerative colitis (UC). The aim of this study was to clarify the profiles of proinflammatory cytokine production in patients with UC in terms of disease intractability, endoscopic findings, and host response to lipopolysaccharide (LPS) stimulation. Colonic mucosal tissues were obtained from patients with active UC (n = 15, including 4 patients with intractable disease) and inactive UC (n = 7), non-inflammatory bowel disease (IBD) colitis (n = 11), and controls (n = 20). Organ culture was performed, and the amounts of four cytokines (described below) in the culture media were determined by enzyme-linked immunosorbent assay (ELISA). LPS stimulation enhanced interleukin (IL)-1beta, IL-8, and IL-6 production in colonic specimens from all groups, but enhanced tumor necrosis factor (TNF)-alpha production only in active UC specimens. Levels of IL-6, IL-8, and TNF-alpha were significantly higher in active UC than in non-IBD colitis, and the production of all three of these cytokines was correlated to the endoscopic grade of inflammation. The production of these cytokines was also significantly higher in patients with intractable disease receiving corticosteroids than in patients with non-intractable disease receiving corticosteroids. These results suggest that enhanced production of mucosal proinflammatory cytokines may be implicated in the pathogenesis of UC.
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PMID:Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis. 1020 29

IL-12 modulates Th1 immune response during chronic colitis. Mechanisms regulating IL-12 synthesis in human intestine are poorly understood. The aim of this study was to investigate the effect of IFN-gamma and PGE2 on lipopolysaccharide (LPS)-stimulated LPMC IL-12 production. Normal LPMC cultures were run in the presence or absence of IFN-gamma and/or PGE2 before LPS stimulation. To examine the role of endogenous PGE2 on LPS-stimulated IL-12 release, LPMC cultures were added of indomethacin before LPS stimulation. IL-12, IL-10 and IL-8 were measured by ELISA. No IL-12 was detected in either unstimulated or LPS-stimulated LPMC cultures. In contrast, LPMC released IL-8 (650 +/- 125 pg/ml) and IL-10 (75 +/- 25 pg/ml) in response to LPS. Treatment of LPMC with IFN-gamma facilitated LPS-stimulated IL-12, whereas it completely abrogated IL-10 production. IL-12 release by LPMC stimulated with IFN-gamma and LPS was significantly inhibited by exogenous IL-10. The addition of PGE2 to IFN-gamma-treated LPMC cultures inhibited in a dose-dependent manner LPS-induced IL-12 secretion. Furthermore, IL-12 was detectable (85 +/- 25 pg/ml) in the supernatants of LPMC cultures treated with indomethacin and LPS. In contrast to the effect on IL-12, PGE2 significantly augmented LPS-stimulated LPMC IL-10 production. However, the inhibition of IL-12 by PGE2 was only partially reversed by anti-IL-10. In a simplified model of LPS tolerance, we finally showed that monocyte-derived macrophages exhibited reduced IL-12 production after repeat LPS stimulation. In these cell cultures, indomethacin abrogated the induction of LPS desensitization. IFN-gamma and PGE2 modulate differently the LPMC responsiveness to LPS in terms of IL-12 synthesis.
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PMID:Interferon-gamma (IFN-gamma) and prostaglandin E2 (PGE2) regulate differently IL-12 production in human intestinal lamina propria mononuclear cells (LPMC). 1046 49


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