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Budesonide Treatment of Patients With Collagenous Colitis Restores Normal Eosinophil and T-cell Activity in the Colon
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Gastroenterology research group)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Gastroenterology research group)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Gastroenterology research group)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2010 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 16, no 7, 1118-1126 p.Article in journal (Refereed) Published
Abstract [en]

Objective: The aim of this study was to assess the activity of eosinophils, neutrophils and CD4+ as well as CD8+ T-cells in eleven patients with active collagenous colitis (CC) before and after eight weeks of budesonide treatment (9 mg once daily) compared to ten healthy individuals.

Methods: Clinical symptoms were recorded and intestinal biopsy samples were taken and analysed by flow cytometry. Eosinophils with a high surface expression of CD44 and low CD9 expression were classified as activated. Neutrophil activity was assessed by their expression of CD66b and CD69 was used as an activation marker for T cells.

Results: All patients responded to the treatment. The eosinophils in active CC showed increased activity compared to controls. The activity was back to control levels after treatment. Neutrophils were not activated in CC patients before or after treatment.

CD8+ T cells from untreated CC patients had a lower activity than controls, and a tendency of lower activity was observed on CD4+ T cells. After treatment, the activity was increased on both types of T cells and was not different from controls.

Conclusions: In the present study we demonstrated that the inflammation in CC is characterized by activated eosinophils but there is no neutrophil activity. CD4+ and CD8+ T cells are increased in numbers in active CC but, surprisingly, they had a lower grade of activity than in control subjects. The major finding in this study is that budesonide treatment restores the normal activation of eosinophils and T-cells, accompanied by clinical remission.

Place, publisher, year, edition, pages
2010. Vol. 16, no 7, 1118-1126 p.
Keyword [en]
Eosinophil, T-lymphocyte, collagenous colitis, budesonide, flow cytometry
National Category
Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:uu:diva-123037DOI: 10.1002/ibd.21188ISI: 000279718800009PubMedID: 20027654OAI: oai:DiVA.org:uu-123037DiVA: diva2:311704
Available from: 2010-04-22 Created: 2010-04-22 Last updated: 2015-05-22Bibliographically approved
In thesis
1. Clinical and Experimental Studies on Inflammatory Bowel Disease with special emphasis on Collagenous Colitis
Open this publication in new window or tab >>Clinical and Experimental Studies on Inflammatory Bowel Disease with special emphasis on Collagenous Colitis
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes studies in patients with inflammatory bowel disease (IBD) and collagenous colitis (CC). We investigated mucosal eosinophil and neutrophil granulocytes and T-cells involved in the inflammatory processes and aimed at determining whether these processes are reflected in the faecal (F) contents of specific proteins secreted by cells in the intestinal mucosa. Thus, we measured eosinophil cationic protein (ECP) and eosinophil protein X (EPX) and the neutrophil derived myeloperoxidase (MPO) and calprotectin (C); and in addition, chromogranin A (CgA), Chromogranin B (CgB) and secretoneurin (SN), derived from EEC cells and cells in the enteric nervous system.

We found that a normalised FC level can serve as a surrogate marker for successful treatment in patients with IBD, but persistently high FC levels need further evaluation (study I). Furthermore, FC and F-MPO appear to relate better than F-EPX to treatment outcome in IBD. We evaluated F-ECP, F-EPX, F-MPO and FC as markers of disease activity and treatment outcome in patients with CC (study III) and concluded that F-ECP was the best discriminator of detecting active CC. Normalised F-ECP and F-EPX could serve as markers of successful treatment. We showed that the inflammation in CC is characterised by activated eosinophils, but that there is no neutrophil activity (study II). T-cells have a lower grade of activity in active CC than in control subjects. During budesonide treatment the normal activation of eosinophils and T-cells is restored, with concomitant clinical remission. The findings in studies II and III indicate that the eosinophils have an essential role in the pathophysiology of CC. Markedly higher values of F-CgA, F-CgB and F-SN were found in patients with CC than in those with IBD and controls (study IV) indicating a crucial role for the intestinal neuro-endocrine system in the pathogenesis of collagenous colitis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 75 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 565
Keyword
Collagenous colitis, inflammatory bowel disease, ulcerative colitis, Crohn´s disease, faecal markers, eosinophil, T-cells, ECP, EPX, MPO, calprotectin, flowcytometry, chromogranin A, chromogranin B, secretoneurin, budesonide
National Category
Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-123053 (URN)978-91-554-7817-9 (ISBN)
Public defence
2010-05-29, Robergsalen, ingång 40, plan 4, Akademiska sjukhuset, UPPSALA, 09:15 (Swedish)
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Available from: 2010-05-07 Created: 2010-04-22 Last updated: 2010-05-18Bibliographically approved

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Wagner, MichaelLampinen, Maria

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