Eosinophils Display an Activated Phenotype in Clinically Active 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. Eosinophils may lead to symptoms through the release of toxic cationic proteins, or contribute to remodelling through the release of TGF-ß.

Aim: The aim of this study was to evaluate the phenotype of eosinophils in large bowel mucosa of patients (1) with symptomatic active disease that was responsive to treatment, {n=6} (2) refractory to treatment, {n=15} and (3) controls, {n=10}. Eosinophil numbers, release of cationic major basic protein (MBP) and expression of TGF- ß were determined.

Methods: Formalin-fixed, paraffin-embedded tissue from these patient groups was studied. Eosinophils were identified using a polyclonal anti-rabbit antibody to eosinophil MBP followed by detection using a peroxidase linked chromagen. The use of this antibody allowed intact, as well as degranulating eosinophils to be identified. TGF-ß was detected using a mouse anti-human monoclonal antibody and sections were counterstained with haemotoxylin to identify eosinophils.

Results: The number of eosinophils was significantly increased in patients with IBD compared with controls. Release of extracellular MBP was seen most markedly in active UC and to a lesser extent in CD before corticosteroid treatment. In contrast, in corticosteroid refractory IBD, while there was considerable increase in the number of eosinophils, there was no release of MBP and only a small proportion of these cells(1%) were TGF-ß positive.

Conclusion: Significant eosinophil accumulation is seen in IBD. Degranulation rates vary with disease activity. A potential therapeutic role of eosinophil inhibition remains to be explored.