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- Carlson, Marie, et al.
(author)
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Increased intraluminal release of eosinophil granule proteins EPO, ECP, EPX, and cytokines in ulcerative colitis and proctitis in segmental perfusion
- 1999
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 94:7, s. 1876-1883
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The role of the eosinophil granulocyte in bowel mucosa in inflammatory bowel disease still remains obscure. The present study was performed in order to elucidate the local eosinophil activity and activating cytokines in the inflamed lesions of colon and rectum in patients with ulcerative colitis and proctitis. METHODS: The activity of intestinal eosinophils with respect to the release of granule proteins was studied in 18 patients (10 with colitis and 8 with isolated proctitis) and 18 healthy controls, using intraluminal segmental perfusion of the sigmoid colon and rectum. The released amounts of eosinophil granule proteins: eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil protein X (EPX) to perfusion fluid were determined by radioimmunoassays. The intraluminal release of possible eosinophil priming cytokines granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 8 (IL-8), were analyzed by immunoassays. RESULTS: The mucosal release of ECP, EPO, and EPX was increased 10- to 20-fold in patients with colitis and proctitis compared with controls. The intraluminal release of GM-CSF and IL-8, was several-fold enhanced in patients with colitis and proctitis. We also found a correlation between all three eosinophil granule proteins and the levels of IL-8/GM-CSF in the sigmoidal segments of patients with colitis. CONCLUSIONS: We conclude that the increased release of ECP, EPO, and EPX to colorectal perfusion fluid indicate eosinophil involvement in the local disease in patients with colitis and proctitis. IL-8 and GM-CSF may play a role in eosinophil accumulation and priming in colitis.
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- Sangfelt, Per, et al.
(author)
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Local release of human neutrophil lipocalin (HNL), IL-8, and TNF-alpha is decreased as response to topical prednisolone treatment in distal ulcerative colitis and proctitis
- 2002
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In: Digestive Diseases and Sciences. - 0163-2116 .- 1573-2568. ; 47:9, s. 2064-2069
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Journal article (peer-reviewed)abstract
- The local release of human neutrophil lipocalin, considered to be highly specific for neutrophil granulocyte activation, and interleukin-8 and tumor necrosis factor-a were studied in 11 patients with distal ulcerative colitis and proctitis before and during treatment with steroid enemas. A rectal perfusion technique for sampling and specific immunoassays for analysis were used. In responders (N = 8) the concentrations of all proteins decreased during the study. There was a close correlation between human neutrophil lipocalin concentrations and treatment response. Tumor necrosis factor-a showed an initial decline in concentrations irrespective of treatment outcome and preceded the decline of human neutrophil lipocalin and interleukin-8. We conclude that decreased neutrophil degranulation is correlated with treatment outcome. Furthermore, an important role of tumor necrosis factor-a in the process of stimulating neutrophil activation and degranulation in ulcerative colitis is suggested.
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- Taha, Yesuf Ahmed, 1951-
(author)
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Collagenous Colitis : A Study of Inflammatory Mediators and Growth Factors Based on Segmental Colorectal Perfusion and Immunohistochemistry
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Collagenous colitis (CC) is an inflammatory bowel disease of unknown etiology. It is characterized by watery diarrhoea without blood, normal endoscopic findings but microscopically colonic mucosal inflammation and increased thickness of the subepithelial collagen band, the latter being a pathognomonic sign. The inflammatory infiltrate in the mucosa of CC contains lymphocytes, plasma cells, eosinophils, mast cells but few neutrophils. The pathophysiological roles of the thickened collagen band and the inflammatory infiltrate in CC are not fully understood. The aims of the present study were to develop a colonoscope based segmental perfusions technique and to analyze local intestinal secretion of inflammatory mediators: Eosinophilic Cationic Protein (ECP), Myeloperoxidase (MPO), Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) and permeability marker albumin in CC patients without medication and also during steroid treatment. Furthermore, the colonic mucosal distribution of bFGF and VEGF were studied by immunohistochemical methods.Colonoscope-based segmental perfusions were performed in totally 22 patients and the success rate was 76% in both rectal and descending colon segments. The analysis showed high intraluminal concentrations of ECP, bFGF, VEGF and albumin in ten CC patients compared to 10 control patients. Further, albumin had correlations with ECP and VEGF. However, elevated concentrations of MPO, an important feature of ulcerative colitis, were only observed in a few CC patients. Immunohistochemistry visualized bFGF and VEGF in the colonic epithelium but also deeper in the lamina propria. The steroid treatment study (including 12 patients) showed that the perfusate concentrations of ECP, bFGF and VEGF declined significantly in parallel with decreased frequency of diarrhoea. In conclusion, a safe colonoscope-based, segmental perfusion technique was developed and perfusions of the rectum and descending colon were performed. CC patients had elevated perfusate concentrations of ECP, VEGF and bFGF. There was a marked reduction of these mediators during steroid treatment supporting the hypothesis that these inflammatory mediators separately or synergistically participate in the inflammatory reaction and tissue remodelling in CC patients. The finding of correlations between albumin and ECP or VEGF implies that permeability is increased in CC and may be triggered by ECP and VEGF.
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- Taha, Yesuf, et al.
(author)
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Steroids reduce local inflammatory mediator secretion and mucosal permeability in collagenous colitis patients
- 2006
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In: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 12:43, s. 7012-7018
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Journal article (peer-reviewed)abstract
- AIM: To study the effect of oral steroids upon clinical response and rectal mucosa secretion of eosinophil cationic protein (ECP), myeloperoxiclase (MPO), basic fibroblast growth factor (bFGF), vascular enclothelial growth factor (VEGF) and albumin in patients with collagenous colitis (CC). METHODS: A segmental perfusion technique was used to collect perfusates from rectum of CC patients once before and twice (one and four weeks) after the start of steroid treatment. Clinical data was monitored and ECP, MPO, bFGF, VEGF and albumin concentrations were analyzed by immunochernical methods in perfusates and in serum. RESULTS: Steroids reduced the number of bowel movements by more than five times within one week and all patients reported improved subjective wellbeing at wk 1 and 4. At the same time, the median concentrations of ECP, bFGF, VEGF and albumin in rectal perfusates decreased significantly. MPO values were above the detection limit in only 3 patients before treatment and in none during treatment. VEGF, bFGF, ECP and albumin concentrations correlated with each other with the exception of ECP and albumin. A decrease of serum ECP and VEGF concentrations was also seen even if the overtime reduction was not significant. CONCLUSION: Oral steroid treatment in CC patients induced a simultaneous reduction of bowel movements and rectal release of ECP, bFGF, VEGF and albumin, suggesting that these polypeptides and increased mucosal permeability are important components of the pathophysiology in collagenous colitis.
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