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Yesuf Taha, Yngve Raab, Anders Larsson, Mikael Lördal, Marie Carlson, Lars Lööf, Magnus Thörn. Steroid Treatment Reduces local Inflammatory Mediator Secretion and Mucosal Permeabil-ity in Collagenous Colitis Patients.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
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Article in journal (Refereed) Submitted
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URN: urn:nbn:se:uu:diva-94225OAI: oai:DiVA.org:uu-94225DiVA: diva2:168005
Available from: 2006-04-06 Created: 2006-04-06Bibliographically approved
In thesis
1. Collagenous Colitis: A Study of Inflammatory Mediators and Growth Factors Based on Segmental Colorectal Perfusion and Immunohistochemistry
Open this publication in new window or tab >>Collagenous Colitis: A Study of Inflammatory Mediators and Growth Factors Based on Segmental Colorectal Perfusion and Immunohistochemistry
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 61 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 130
Keyword
General, Collagenous, Collagenous colitis, inflammatory mediators, Steroid treatment, Eosinophil Cationic Protein, Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF), albumin, ALLMÄNT
Identifiers
urn:nbn:se:uu:diva-6736 (URN)91-554-6510-2 (ISBN)
Public defence
2006-04-27, Robergsalen, Ingång 40, 4 tr, Akademiska Sjukhuset, Uppsala, 13:15
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Available from: 2006-04-06 Created: 2006-04-06Bibliographically approved

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