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Collagenous Colitis: A Study of Inflammatory Mediators and Growth Factors Based on Segmental Colorectal Perfusion and Immunohistochemistry
Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
2006 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis , 2006. , s. 61
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 130
Nyckelord [en]
General, Collagenous, Collagenous colitis, inflammatory mediators, Steroid treatment, Eosinophil Cationic Protein, Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF), albumin
Nyckelord [sv]
ALLMÄNT
Identifikatorer
URN: urn:nbn:se:uu:diva-6736ISBN: 91-554-6510-2 (tryckt)OAI: oai:DiVA.org:uu-6736DiVA, id: diva2:168006
Disputation
2006-04-27, Robergsalen, Ingång 40, 4 tr, Akademiska Sjukhuset, Uppsala, 13:15
Opponent
Handledare
Tillgänglig från: 2006-04-06 Skapad: 2006-04-06Bibliografiskt granskad
Delarbeten
1. Evidence of local eosinophil activation and altered muco-sal permeability in collagenous colitis.
Öppna denna publikation i ny flik eller fönster >>Evidence of local eosinophil activation and altered muco-sal permeability in collagenous colitis.
Visa övriga...
2001 Ingår i: Dig Dis Sci, Vol. 46, s. 888-97Artikel i tidskrift (Refereegranskat) Published
Identifikatorer
urn:nbn:se:uu:diva-94222 (URN)
Tillgänglig från: 2006-04-06 Skapad: 2006-04-06Bibliografiskt granskad
2. Mucosal secretion and ex-pression of basic fibroblast growth factor in patients with colla-genous colitis.
Öppna denna publikation i ny flik eller fönster >>Mucosal secretion and ex-pression of basic fibroblast growth factor in patients with colla-genous colitis.
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2003 Ingår i: Am J Gastroenterol, s. 2011-7Artikel i tidskrift (Refereegranskat) Published
Identifikatorer
urn:nbn:se:uu:diva-94223 (URN)
Tillgänglig från: 2006-04-06 Skapad: 2006-04-06 Senast uppdaterad: 2015-03-17Bibliografiskt granskad
3. Vascular Endothelial Growth Factor (VEGF) - A possible mediator of inflammation and mucosal permeability in patients with collagenous colitis.
Öppna denna publikation i ny flik eller fönster >>Vascular Endothelial Growth Factor (VEGF) - A possible mediator of inflammation and mucosal permeability in patients with collagenous colitis.
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2004 Ingår i: Dig Dis Sci, s. 109-115Artikel i tidskrift (Refereegranskat) Published
Identifikatorer
urn:nbn:se:uu:diva-94224 (URN)
Tillgänglig från: 2006-04-06 Skapad: 2006-04-06 Senast uppdaterad: 2015-03-17Bibliografiskt granskad
4. 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.
Öppna denna publikation i ny flik eller fönster >>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.
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Artikel i tidskrift (Refereegranskat) Submitted
Identifikatorer
urn:nbn:se:uu:diva-94225 (URN)
Tillgänglig från: 2006-04-06 Skapad: 2006-04-06Bibliografiskt granskad

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