Inflammatory cytokines in small intestinal mucosa of patients with potential coeliac disease

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Abstract
T helper cell type 1 (Th1) response to gluten has been implicated in the pathogenesis of coeliac disease (CD). To characterize immunological activation and mild inflammations leading to overt CD in potential coeliac patients, jejunal biopsies were obtained from family members of patients with CD or dermatitis herpetiformis (DH). Nine family members and one latent CD, eight CD patients and eight normal controls furnished jejunal biopsy specimens. Immunohistochemical staining of sections for interleukin-1α (IL-1α), IL-2, IL-4, interferon-γ (IFN-γ), tumour necrosis factor α (TNF-α), CD3, γδ-T cell receptor (γδ-TCR), and αβ-TCR was carried out with monoclonal antibodies. Further, expression of IL-4 and IFN-γ messenger RNA was detected by radioactive in situ hybridization in these same samples. In lamina propria, CD patients and potential CD patients had higher densities of IL-2 (P = 0·028, P = 0·043), IL-4 (P = 0·021, P = 0·034) and IFN-γ positive cells (P = 0·000, P = 0·009) than did controls. Moreover, CD patients showed a higher density of TNF-α positive cells (P = 0·012, P = 0·001) than the other two groups, and expression of IFN-γ mRNA (P = 0·035) was higher in them than in the other two study groups. Additionally, higher densities of TNF-α and IFN-γ positive cells occurred in potential CD patients with high γδ-TCR+ intraepithelial lymphocytes (IELs). Our findings support the hypothesis that lamina propria T cells and macrophages, through their secretion of cytokines, play a central role in the pathogenesis of coeliac disease. The inflammatory cytokines found in potential CD specimens strongly suggest that these inflammatory markers can be identified long before visible villous changes have occurred.