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Gut mucosal granulocyte activation precedes nitric oxide production:  studies in coeliac patients challenged with gluten and corn
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
2005 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 54, no 6, 769-774 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: To elucidate the dynamics of nitric oxide (NO) production induced by rectal gluten challenge and the relation between NO production and mucosal granulocyte activation. Subjects and

METHODS: Release of rectal NO was measured in 13 patients with coeliac disease and in 18 controls before and after rectal wheat gluten challenge. Rectal gas was collected with a rectal balloon using a newly developed instrument/technique, the "mucosal patch technique". The instrument allows simultaneous measurements of concentrations of granulocyte mediators in the rectal mucosa. We measured myeloperoxidase (MPO), eosinophil cationic protein (ECP), and histamine. For comparison, we made similar measurements after corn (maize) gluten challenge.

RESULTS: In all coeliac patients rectal NO concentration increased after gluten challenge and reached a peak after 15 hours (mean 9464 (SEM 2393) parts per billion (ppb); range 250-24982). The maximum MPO and ECP increase occurred five hours after challenge. A correlation was found between mucosal MPO and NO production at 15 hours. Six of the patients showed an increase in NO production 15 hours after rectal corn gluten challenge but this was much smaller than after gluten challenge. No increases were seen in the control group after either challenge.

CONCLUSION: Mucosal activation of neutrophils and eosinophils precedes pronounced enhancement of mucosal NO production after rectal wheat gluten challenge in patients with coeliac disease. Some of our coeliac patients displayed signs of an inflammatory reaction, as measured by NO and granulocyte markers, after rectal corn gluten challenge.

Place, publisher, year, edition, pages
2005. Vol. 54, no 6, 769-774 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-93626DOI: 10.1136/gut.2004.057174PubMedID: 15888782OAI: oai:DiVA.org:uu-93626DiVA: diva2:167159
Available from: 2005-10-20 Created: 2005-10-20 Last updated: 2010-11-30Bibliographically approved
In thesis
1. Food Antigen Sensitivity in Coeliac Disease Assessed by the Mucosal Patch Technique
Open this publication in new window or tab >>Food Antigen Sensitivity in Coeliac Disease Assessed by the Mucosal Patch Technique
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A diagnosis of coeliac disease (CD) in adults relies on the presence of a structurally abnormal intestinal mucosa, followed by a clear clinical remission on a gluten-free diet. There is a clear need for a rapid, simple, safe and sensitive method to determine the type and intensity of inflammation in the gut mucosa in clinical practice. The overall aims of our studies were to develop and evaluate a new technique, “the mucosal patch technique”, to characterize rectal local inflammatory process after rectal food challenge in patients with CD. In study 1 we evaluated the potential of the new technique. The technique was well tolerated and easily applied. Pronounced neutrophil and eosinophil involvement in ulcerative colitis (UC) was demonstrated. With the high sensitivity of the technique, low-degree mucosal neutrophil activation could also be quantified in patients with collagen colitis,UC in clinical remission and in patients with irritable bowel syndrome. In study 2 and 3 the aim was to elucidate the dynamics of the rectal inflammatory response and nitric oxide (NO) production after rectal gluten challenge. We found a pronounced neutrophil activation in coeliac patients after rectal gluten challenge. This activation was apparent 4 hours after challenge and remains for at least 48 hours. A more modest eosinophil activation started 1-2 hours later and remained at least for 48 hours. The biphasic pattern of neutrophil and eosinonphil activation after challenge suggests a biphasic inflammatory reaction. The activation of neutrophils and eosinophils precedes a pronounced enhancement of mucosal NO production. Some of our coeliac patients displayed signs of an inflammatory reaction after rectal corn gluten challenge. In study 4 the aim was to investigate the local inflammatory reaction to gluten and cow’s milk protein in CD patients in remission. The findings indicate that not only gluten sensitivity but also cow’s milk (CM) protein sensitivity is common in CD. The data support the hypothesis that CM sensitivity may contribute to persistent symptoms in coeliac patients on gluten-free diet.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 69 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 80
Medicine, Coeliac disease, Diagnostic instrument, food hypersensitivity, gut pathophysiologi, inflammation, nitric oxide, rectal instillation, gluten, corn, milk hypersensitivity, inflammatory bowel disease, irritable bowel syndrome, Medicin
National Category
Dermatology and Venereal Diseases
urn:nbn:se:uu:diva-6020 (URN)91-554-6374-6 (ISBN)
Public defence
2005-11-11, Grönwallssalen, Uppsala Akademiska Sjukhus, Uppsala, 09:15
Available from: 2005-10-20 Created: 2005-10-20Bibliographically approved

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