Localization of Eosinophils to Different Subspecies of Nerves in Inflammatory Bowel Disease

Introduction: The role of the eosinophil, which is a common inflammatory cell in inflamed gastrointestinal mucosa in inflammatory bowel disease (IBD) is uncertain. Many of the symptoms of IBD are due to neural dysregulation, including increased mucous production and dysmotility. We hypothesized that an interaction between eosinophils and nerves may explain how inflammation is related to neural dysfunction in IBD. The aim of this study was to determine the interaction of eosinophils with nerves in IBD, and to define the type of nerves involved.

Methods: Using formalin-fixed paraffin-embedded tissue from patients who had previously undergone colonic resection for intractable symptoms of IBD, the inter-relationship of eosinophils and enteric nerves was assessed. Using double immunohistochemical staining techniques, eosinophils were identified using an antibody to Major Basic Protein (MBP) and nerves were sub-typed using antibodies to S100, Substance P, Nitric oxide synthase (nNOS) and Choline acetyltransferase (ChAT).

Results: Eosinophils selectively localize to nerves in the mucosal layer of patients with Crohn's disease (CD) (p<0.001) and ulcerative colitis (UC) (p<0.01). Eosinophils also selectively localize to nerves in the muscle layer of patients with both CD and UC, although to a lesser degree in UC (P<0.05). Furthermore, eosinophils localize to specific nerve subtypes, namely Substance P and ChAT containing nerves but not nNOS containing nerves.

Conclusion: Eosinophils localize to specific nerve subtypes in patients with active IBD. Interactions between these cells may influence both nerve and eosinophil function.