GLUTEN INDUCES AN INTESTINAL CYTOKINE RESPONSE STRONGLY DOMINATED BY INTERFERON-GAMMA IN PATIENTS WITH CELIAC-DISEASE

Background & Aims: Celiac disease appears to be a T cell-mediated ente ropathy induced by gluten in genetically predisposed individuals. Duod enal biopsy specimens from patients with celiac disease and histologic ally normal controls were investigated to see if cytokine expression i s related to disease activity. Methods: Cytokine messenger RNA (mRNA) expression was determined by quantitative reverse-transcription polyme rase chain reaction and in situ expression by immunohistochemistry. Re sults: In normal controls, mRNA levels were usually below the quantita tive limit, even after in vitro gluten stimulation. By contrast, inter feron (IFN)-gamma mRNA was increased more than 1000-fold in untreated disease. In vitro gluten stimulation of specimens from treated patient s (gluten-free diet) increased IFN-gamma mRNA to the levels of untreat ed patients. In addition, increased mRNA levels for interleukin (IL)-2 , IL-4, IL-6, and tumor necrosis factor alpha were found after such st imulation, whereas mRNA for IL-5, IL-10, and IL-12p40 was usually belo w the quantitative level. Biopsy specimens from untreated patients con tained on average 10-fold more lamina propria cells positive for IFN-g amma 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-gamma expression and lower levels of IL-2, IL-4, IL-6, and tumo r necrosis factor alpha even in the virtual absence of IL-12.