The role of eosinophils in inflammatory bowel disease

Eosinophils are proinflammatory leucocytes that constitute a small percentage of circulating blood cells. In the healthy state, most of these cells reside in the gastrointestinal tract within the lamina propria of the stomach and intestine. They differentiate in the bone marrow from progenitor cells under the influence of interleukin (IL)-3, IL-5, and granulocyte-macrophage colony stimulating factor. IL-5 also stimulates their release into the peripheral circulation. ¹ They then migrate to the gastrointestinal tract in response to eotaxin, a chemokine that is constitutively expressed throughout the gastrointestinal tract. This chemokine binds to the CCR-3 receptor on eosinophils and is required for their homing to the gastrointestinal tract. ^{2, 3} However, constitutive expression of eotaxin is not sufficient for tissue eosinophil trafficking because some gastrointestinal segments (such as the tongue and oesophagus) express eotaxin but are normally devoid of eosinophils. ¹ So this may explain why the help of other cytokines is needed to complete the homing of eosinophils to the intestines. One such cytokine is IL-5, which increases the circulating pool of eosinophils and primes eosinophils to have enhanced responses to eotaxin. ¹

Eosinophils secrete toxic inflammatory mediators that are stored in preformed vesicles and also synthesised de novo following cellular activation. The major proteins secreted by eosinophils are eosinophilic cationic protein, major basic protein, eosinophil protein X, eosinophil derived neuroendotoxin, and eosinophil peroxidase. These cause damage to tissues, insert pores into membranes of target cells, and increase smooth muscle reactivity by generating toxic oxygen radicals. ⁴

Eosinophils and the role they play in inflammatory diseases of the gastrointestinal tract have become a point of interest in recent literature. Inflammatory bowel disease (IBD) includes two major chronic diarrhoeal illnesses, ulcerative colitis (UC) and Crohn's disease (CD). The inflammatory process in these illnesses involves many inflammatory cells, such as lymphocytes, macrophages, mast cells, neutrophils, and eosinophils. ⁵ The two most important roles that eosinophils play in IBD appear to be as proinflammatory and promotility agents thus producing effects such as diarrhoea, inflammation, tissue destruction, formation of fibrosis and strictures and, as recently suggested, even repair. ⁶

IBD probably starts by an unknown antigenic stimulus likely coupled with genetic predisposition that leads to increased production in the intestinal tract of chemoattractants to a variety of inflammatory cells,...