Increased Number and Activation of Colonic Macrophages in Pediatric Patients with Untreated Crohn's Disease

Background: Pediatric inflammatory bowel disease (IBD) may be phenotypically different from adult IBD. In IBD lesions, macrophages are overactivated. suggesting involvement of innate immunity in the pathogenesis. Here, mucosal macrophages were Studied in selected Untreated Pediatric patients compared with adults front a population-based Norwegian cohort of IBD patients. Age-matched non-IBD controls were also included. Methods: Untreated children (<18 years) and adults (>= 18 years) were included at diagnosis, with colonic and ileal biopsies. Controls were symptomatic non-IBD patients with histologically normal gut. Frozen mucosal sections were examined by immunohistochemistry, for Cellular expression of the pan-macrophage marker CD68 and the costimullatory molecule CD40. Two-color immunofluorescence staining in situ was performed to identify CD40(+) macrophages. Results: Non-IBD adults had significantly higher mucosal density of colonic CD68(+) macrophages than non-IBD children. Ill Pediatric Crohn's disease (CD), macrophages were significantly increased in the colon (but not ill the ileum) compared with controls. Their mucosal density in pediatric CD was significantly higher than in Pediatric ulcerative colitis. The number of CD40(+) (activated) macrophages was significantly elevated in both histologically inflamed and uninflamed colon and ileum of IBD children. Conclusions: Histologically normal colon mucosa contains fewer macrophages in children than in adults. However, in colon of children with Untreated CD the mucosal macrophage density is increased. Activated mucosal macrophages are increased in untreated Pediatric IBD regardless of inflammatory grade. Such upregulated innate mucosal immune activation may contribute to the colonic phenotype of childhood CD.