title: Cytokine tissue levels as markers of disease activity in pediatric Crohn disease.
abstract: The mucosal immune system is overactivated in Crohn disease (CD) and viral infections have been associated with clinical exacerbations. To investigate the potential association between mucosal inflammation and the cytokines involved in the early response to viruses, we analyzed colonic tissue levels of IL-2Ralpha, interferon-alpha, and IL-15 in CD. Patients undergoing diagnostic colonoscopy were classified into controls (n = 22) and three CD groups based on the histologic severity of inflammation and clinical activity: a) severely active CD (n = 3); b) mild to moderately active CD (n = 14); and c) quiescent CD (n = 23). Rectal biopsies (two per patient) were homogenized and cytokine levels determined by ELISA kits. Statistical analysis was performed by ANOVA with Tukey and Scheffé tests. IL-2Ralpha levels were increased in the active CD group compared with the quiescent CD group: a) 405 +/- 87, b) 159 +/- 31, and c) 33 +/- 15 pg/mg DNA (p < 0.001). The latter group was similar to controls (39 +/- 20 pg/mg DNA). Furthermore, a linear correlation (r = 0.98) between IL-2Ralpha and disease activity (Van Hees index) was observed. IL-15 levels were also higher in active compared with quiescent CD and controls: a) 0.69 +/- 0.23 and b) 0.72 +/- 0.31 versus c) 0.28 +/- 0.21 and 0.28 +/- 0.14 pg/mg DNA for controls (p < 0.05). Interferon-alpha levels were undetectable in all samples. Our data suggest that IL-2Ralpha tissue levels correlate with CD activity. IL-15 is also overproduced in inflamed CD tissue. The lack of a parallel elevation of interferon-alpha does not support a role for viral induction of IL-15 in inflamed CD samples.
authors.affiliation: Mucosal Immunology Laboratory, Division of Gastroenterology, Hepatology and Nutrition, Sainte-Justine Hospital Research Center, Montréal, Quebec, Canada.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Silva
authors.forename: José
authors.initials: J
authors.lastname: Menezes
authors.forename: Sarah
authors.initials: S
authors.lastname: Wizman
authors.forename: Roxanne
authors.initials: R
authors.lastname: Gendron
authors.forename: Luc
authors.initials: L
authors.lastname: Oligny
authors.forename: Ernest G
authors.initials: EG
authors.lastname: Seidman
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism*; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit; D008297:Male; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C508017:IL2RA protein, human; D016898:Interferon-alpha; D019409:Interleukin-15; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin