The Role of Eosinophils and Mast Cells in Intestinal Functional Disease

Abstract

Functional gastrointestinal disorders (FGIDs) are common and currently defined by a symptom-based classification with no discernable pathology. In functional dyspepsia (FD), the duodenum is now implicated as a key area where symptoms originate.This is attributed to immune activation with increasing evidence indicating a role for duodenal eosinophilia. In irritable bowel syndrome (IBS), mastocytosis has been documented throughout the small and large intestine. Eosinophils and mast cells are an important link between innate and adaptive immunity, and are important in allergic type TH2 inflammation. Eosinophils may give rise to symptoms due to release of preformed cytokine proteins, which trigger neural excitation, muscle spasm, and pain. The close relationship of mast cells to nerves in IBS may similarly give rise to symptoms. Genetic studies also support of the role of innate immunity in FGIDs. The data supporting a prime role for eosinophils and mast cells in subsets of FD and IBS has become credible, and these data should be used to implement advances in diagnosis and therapeutic trials.

A biomarker panel and psychological morbidity differentiates the irritable bowel syndrome from health and provides novel pathophysiological leads

“…39 Histamine may reflect mast cell dysfunction, also known to be a key pathophysiological marker in IBS. 40,41 The highly novel data presented here in turn suggest that IBS subtypes represent entities that are to some extent biologically distinct. IBS is likely a heterogenous disorder making identification of unique biomarkers potentially extremely challenging.…”

Analysis of Gastric and Duodenal Eosinophils in Children with Abdominal Pain Related Functional Gastrointestinal Disorders According to Rome III Criteria

“…16,46 With the release of cytokines, such as IL-4, IL-5, and IL-13 from type 2 T helper cells during the inflammatory response, activated eosinophils are ready for massive degranulation. 11,16,20,47 Degranulation contents, such as the nerve growth factor, have a direct influence on sensory nerves, and major basic proteins can induce vagal nerve muscarinic receptor 2 dysfunction. 19,20 Platelet aggregating factor, leukotrienes, and IL-13 are also able to act directly on the smooth muscle cells, thereby increasing contractility and reactivity.…”

“…Duodenal eosinophilia can be associated with an allergy, 20 and eosinophils in the duodenum can be activated in patients with allergy-related disorders, including asthma and atopic eczema, which can induce gastrointestinal symptoms in these groups of patients. 11,50,51 To eliminate the factors which can affect eosinophil activation in the gastrointestinal tract, we excluded in the present study patients who had a significant allergy, including food allergy, asthma, atopic dermatitis, and allergic rhinitis.…”

“…[6][7][8][9][10] Recent studies suggest that mild inflammation of the intestines is essentially involved in the pathophysiology of functional gastrointestinal disorder (FGID). [11][12][13][14][15][16] Adult studies on FGID, especially functional dyspepsia (FD) and irritable bowel syndrome (IBS), 13,14 have found that increased infiltration of eosinophils, mast cells, and intraepithelial lymphocytes represent low-grade mucosal inflammation in the gastrointestinal tract. In adult FD patients, gastric eosinophil counts tend not to be significantly increased, but the duodenal eosinophil count and duodenal degranulation is prominently increased.…”

Mast Cells and Intestinal Motility Disorders (Mastocytic Enteritis/Colitis)

“…Amongst these, increased numbers of mast cells (MC), eosinophils, intraepithelial T-lymphocytes and serotonin-producing enterochromaffin cells have attracted the most attention [1,2]. The traditional paradigm of IBS as a ''functional'' disorder may be changing with the possibility of an underlying neuro-immune interaction increasingly being considered.…”