Detection of interferon regulatory factor-1 in lamina propria mononuclear cells in Crohn's disease

Background: The transcription factor, interferon regulatory factor (IRF)-1, is stimulated by interferon-gamma and regulates the expression of several genes implicated in the pathogenesis of inflammatory bowel disease, includi ng interleukin-6, major histocompatibility complex class II molecules, and inducible nitric oxide synthase. Interferon regulatory factor-1 also stimul ates naive CD4+ TT-cells to differentiate into T-helper-l cells, the T-cell subset that appears to be upregulated in Crohn's disease. The purpose of t his study was to examine the expression of IRF-1 in the nuclei of lamina pr opria mononuclear cells in situ in colonoscopic biopsy specimens from pedia tric patients with Crohn's disease, in patients with ulcerative colitis, an d in control patients with no histopathologic abnormalities. Methods: Archival paraffin-embedded tissue sections were obtained from 25 p ediatric patients with Crohn's disease, 6 patients with ulcerative colitis, and 12 control patients who had undergone colonoscopy. Tissue sections wer e stained with polyclonal rabbit anti-human antisera to IRF-1 and horseradi sh-peroxidase-conjugated, biotinylated, goat anti-rabbit secondary antibody . Slides were scored and scores compared among patient groups using analysi s of variance. Results: Patients with Crohn's disease had significantly higher IRF-1 score s (95% confidence interval [CI], 1.70-2.04) than patients with ulcerative c olitis (95% CI, 0.92-1.23) or control subjects (95% CI, 1.11-1.52). Conclusions: Increased expression of IRF-1 in lamina propria mononuclear ce lls from patients with Crohn's disease may be relevant to the pathogenesis of Crohn's disease. (C) 1999 Lippincott Williams & Wilkins, Inc.