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Peripheral blood intracellular cytokine analysis in children newly diagnosed with inflammatory bowel disease
Authors:Mack David R  Beedle Susan  Warren Jame  Davis Jack  Gross Thomas
Institution:Department of Paediatrics, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada, K1H 8L1. dmack@cheo.on.ca
Abstract:Patterns of cytokine profiles have emerged for different forms of inflammatory bowel disease with a predominance of type 1 cytokines in patients with Crohn disease and type 2 cytokine expression in patients with ulcerative colitis. Most of these studies have involved older patients with long-standing disease or after various therapeutic interventions, and patterns of cytokine expression were hypothesized to be influenced by these factors. To evaluate for these possibilities, we studied 23 patients (15 boys) with newly diagnosed Crohn disease (n = 14) or ulcerative colitis. Their mean age at diagnosis was 13.1 +/- 2.9 y (mean +/- SD). Healthy control subjects (n = 9) were previously obtained. Peripheral blood intracellular cytokine analysis was performed within 24 h using a modification of Becton Dickinson's FastImmune Cytokine system. Multiparametric flow cytometry and phenotyping of lymphocytes was performed. T-cell populations were defined as type 1 being CD69(+), CD3(+), and interferon-gamma(+) and type 2 being CD69(+), CD3(+), and IL-4(+). The median percent of type 1 T cells from normal subjects (2.8%) was similar to that of ulcerative colitis subjects (1.8%, p > 0.20) but greater than that of Crohn disease subjects (0.55%, p = 0.05). The median percent of type 2 lymphocytes in normal subjects (1.8%) was greater than that of ulcerative colitis subjects (0.35%, p = 0.02) but was similar to that of Crohn disease subjects (1.1%, p > 0.20). Serial determinations showed the median percent of type 2 T cells increased in ulcerative colitis patients as remission was induced. Reduced activated peripheral type 1 T cells of newly diagnosed, untreated children are similar to interferon-gamma expression in mucosa of adults with postoperative recurrence. Reduced type 2 cytokine expression patterns in subjects with ulcerative colitis are similar to lamina propria T-cell expression levels in adults and improve with disease remission.
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