Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease

EM Nilsen, FL Jahnsen, KEA Lundin, FE Johansen… - Gastroenterology, 1998 - Elsevier
EM Nilsen, FL Jahnsen, KEA Lundin, FE Johansen, O Fausa, LM Sollid, J Jahnsen, H Scott…
Gastroenterology, 1998Elsevier
Background & Aims: Celiac disease appears to be a T cell–mediated enteropathy induced
by gluten in genetically predisposed individuals. Duodenal biopsy specimens from patients
with celiac disease and histologically normal controls were investigated to see if cytokine
expression is related to disease activity. Methods: Cytokine messenger RNA (mRNA)
expression was determined by quantitative reverse-transcription polymerase chain reaction
and in situ expression by immunohistochemistry. Results: In normal controls, mRNA levels …
Background & Aims
Celiac disease appears to be a T cell–mediated enteropathy induced by gluten in genetically predisposed individuals. Duodenal biopsy specimens from patients with celiac disease and histologically normal controls were investigated to see if cytokine expression is related to disease activity.
Methods
Cytokine messenger RNA (mRNA) expression was determined by quantitative reverse-transcription polymerase chain reaction and in situ expression by immunohistochemistry.
Results
In normal controls, mRNA levels were usually below the quantitative limit, even after in vitro gluten stimulation. By contrast, interferon (IFN)-γ mRNA was increased more than 1000-fold in untreated disease. In vitro gluten stimulation of specimens from treated patients (gluten-free diet) increased IFN-γ mRNA to the levels of untreated patients. In addition, increased mRNA levels for interleukin (IL)-2, IL-4, IL-6, and tumor necrosis factor α were found after such stimulation, whereas mRNA for IL-5, IL-10, and IL-12p40 was usually below the quantitative level. Biopsy specimens from untreated patients contained on average 10-fold more lamina propria cells positive for IFN-γ than normal controls, whereas cells containing IL-4 were rare in both subject groups.
Conclusions
The results show that mucosal gluten exposure in patients with celiac disease rapidly elicits high levels of IFN-γ expression and lower levels of IL-2, IL-4, IL-6, and tumor necrosis factor α even in the virtual absence of IL-12. GASTROENTEROLOGY 1998;115:551-563
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