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-2Rα, interferon-α, 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-2Rα 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-2Rα 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-α levels were undetectable in all samples. Our data suggest that IL-2Rα tissue levels correlate with CD activity. IL-15 is also overproduced in inflamed CD tissue. The lack of a parallel elevation of interferon-a does not support a role for viral induction of IL-15 in inflamed CD samples.