Alimentary TractGluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease☆,☆☆
Section snippets
Patients
The patients enrolled in the cytokine mRNA study were evaluated according to the European Society for Pediatric Gastroenterology and Nutrition criteria for celiac disease of 1990.19 Biopsy specimens from the distal duodenum (n = 1–5 per subject) were obtained during upper gastrointestinal endoscopy (Olympus GIF IT20 endoscope; biopsy forceps, Olympus FB 13K; Tokyo, Japan) from 20 patients with celiac disease (median age, 38 years; range, 6–68 years), 7 with untreated disease and 13 on a
Estimation of cytokine mRNA expression by RT-PCR
Intestinal specimens from histologically normal controls, both unstimulated and stimulated in vitro with gluten, were either negative or showed only low expression of IFN-γ, IL-2, IL-4, IL-5, IL-6, and IL-12p40 mRNA. Moreover, we were unable to detect transcripts for IL-10 and TNF-α (Figure 1).
Discussion
Quantification of mRNA levels by RT-PCR showed that the expression of IFN-γ was remarkably increased in the duodenal mucosa of patients with celiac disease after gluten exposure in vivo or in vitro compared with similarly exposed histologically normal control mucosa. Conversely, only low mucosal levels of IL-2, IL-4, IL-5, IL-6, IL-12p40, and TNF-α mRNA were detected even after gluten stimulation, whereas all specimens showed constitutive expression of TGF-β but were negative for IL-10. In
Acknowledgements
The authors thank Aaste Aursjø, Drude Hansson, and Tone Narvesen for excellent technical assistance; Dr. Ø. Molberg for providing T-cell clones; and Dr. M.F. Kagnoff for the generous gift of plasmids to generate standard mRNA. Mabtech AB is acknowledged for covering the costs of the color plate.
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Address requests for reprints to: Ellen M. Nilsen, Ph.D., LIIPAT, Rikshospitalet, N-0027 Oslo, Norway. e-mail: [email protected]; fax: (47) 22112261.
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Supported by the Norwegian Cancer Society, the Research Council of Norway, Anders Jahre's Foundation, the Medinnova Governmental Research Organization, and the Norwegian Celiac Disease Association.