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Granulocyte/monocyte apheresis (GMA) selectively removes circulating granulocytes and monocytes; important producers of proinflammatory cytokines. Seven children with new-onset inflammatory bowel disease (IBD) colitis were treated with GMA together with mesalazine, and had significant decreases in Pediatric UC Activity Index (P = 0.018) and Mayo endoscopic score (P = 0.013). We investigated the colonic mucosal cytokine profiles (analyzed with real-time polymerase chain reaction), before and after induction treatment, and in 6 non-IBD controls. Significant decreases were seen in Colony Stimulating Factor 2 (P = 0.018), tumor necrosis factor-α (P = 0.028), interleukin (IL)-23α (P = 0.043), IL-1β (P = 0.028), IL-36γ (P = 0.018), IL-10 (P = 0.028), and transforming growth factor beta 1 (P = 0.043) after treatment. In 6 non-IBD controls there were significantly lower levels of IL-12β (P = 0.023) and IL-23α (P = 0.046) compared to the patients with IBD at onset, and IL-22 (P = 0.088) and IL-36γ (P = 0.062) showed lower values without reaching significant differences. We speculate that the decreases in colonic mucosal cytokine profiles after treatment may explain the observed clinical efficacy in the GMA-treated children with IBD.