Gut luminal neutrophil migration is influenced by the anatomical site of Crohn's disease

BACKGROUND: Clinical differences between small- and large-bowel Crohn's disease have been demonstrated. Neutrophil migration and degranulation are important effector mechanisms in gut damage. Granulocyte elastase, a neutrophil-bound enzyme, interleukin 8 and 1beta can be detected in whole-gut lavage fluid. We aimed to assess differences between large- and small-bowel Crohn's disease. METHODS: A total of 167 patients with active inflammatory bowel disease (118 Crohn's disease, 49 ulcerative colitis) underwent whole-gut lavage with a polyethylene glycol electrolyte solution. Granulocyte elastase was assayed using an enzyme substrate reaction, IL-8 and IL-1beta by ELISA. RESULTS: Twenty-seven of 36 patients with isolated colonic Crohn's disease had detectable granulocyte elastase (median 0.259 pKat/l, range < 0.039-2.742 microKat/l), whereas 3 of 15 with small-bowel involvement alone had detectable granulocyte elastase (median < 0.039 microKat/l, range < 0.039-0.266 microKat/l; P < 0.0001). Granulocyte elastase levels were significantly higher in patients with ileocolonic disease and post-ileocaecal resection compared with small-bowel disease alone. IL-8 (P< 0.0001) and IL-1beta (P < 0.04) levels differed between colonic and ileal distributions. No variations were seen in ulcerative colitis. CONCLUSIONS: Neutrophil migration to the gut lumen in Crohn's disease is a feature of colonic disease irrespective of associated ileal lesions. This suggests that bacterial-derived chemo-attractants may play a role. High levels of IL-8 in colonic disease are consistent with this hypothesis.