Žarko Babić

Comparison of Cytokine and Efflux Transporter Expression in Pediatric vs. Adult Onset Ulcerative Colitis

Objectives: Ulcerative colitis (UC), a chronic inflammation of the colon, is often more severe in children than adults. Identification of altered expression of efflux transporters, cytokines, and suppressor of cytokine signaling (SOCS) molecules in pediatric versus adult patients could provide insight into the differential molecular patterns related to the age and disease pathology. Methods: Mucosal samples from terminal ileum and colon in pediatric (9 UC-New, 4 UC-Remission) and adult (9 UC-New, 8 UC-Remission) patients were compared with healthy subjects (15 children and 10 adults) for mRNA expressions of several efflux transporters, cytokines, and SOCS molecules. Results: The inflamed colon interleukin (IL)-6, IL-17A, and interferon-&ggr; levels were elevated in UC-New subgroups but close to control values in UC-Remission. IL-1&bgr; expression was increased only in UC-New children. Interestingly, uninflamed ileum also showed increased IL-6 and IL-1&bgr; levels in UC-New subgroups. SOCS1/SOCS3 expression pattern followed a trend observed for inflammatory cytokines only in children. Both children and adults had decreased multidrug resistance protein 1 expression in colon, which inversely correlated with disease score, IL-6 and interferon-&ggr; levels in UC-New children. IL-2 expression was upregulated in UC-Remission, compared with controls. Conclusions: Efflux transporter expression varies between UC children and adults except for decreased multidrug resistance protein 1. UC is characterized by a dysregulated TH1 and TH17 cytokine response irrespective of age at disease onset, with higher cytokine levels detected in children. Increased IL-2 levels in remission imply a protective role for regulatory T cells (Tregs).