Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

Abstract

Irritable bowel syndrome (IBS) is the most common condition seen by gastroenterologists. It presents with alternating symptoms of bowel dysfunction that often worsens with stress. The cause of these symptoms eludes investigators and many attempts have been made to discover an underlying pathology. This is a daunting task since symptoms come and go, and change characteristics. Furthermore, the pathology of IBS is unlikely to be identical in all patients. In addition, all symptoms and all features studied thus far have a strong overlap with healthy volunteers. Elsewhere in this issue, Braak et al. report a well-designed clinical investigation in patients with IBS and come to the conclusion that IBS is not characterized by mast cell or other immune cell proliferation, but by immune dysregulation in the colon. Is this the fi nal answer? Am J Gastroenterol 2012; 107:727 -729; doi: 10.1038/ajg.2012 Irritable bowel syndrome (IBS) is a common functional disorder in the West ( 1 ) and in Asia ( 2 ), which is characterized clinically as abdominal discomfort or pain with alternating constipation and diarrhea. Mechanistic pathways to symptom generation are unclear, although dysfunction of brain-gut communication, gut motility, visceral perception, neuroimmune responses, infl ammation, and mucosal integrity, as well as the psychosocial status might be involved ( 3 ). Th e mucosa contains endings of the enteric sensory nerves; these aff erent nerves can modify motility and pain perception. Th erefore, immune cell infi ltration assessed in mucosal biopsies may provide critical information on the mechanisms of symptom generation. Both intestinal ( 4 ) and colonic ( 5,6 ) biopsies have been investigated. Mast cells have received particular attention because its secretory products, such as histamine, prostaglandins, and proteinases, are capable of sensorimotor dysfunction. IBS appears to worsen with stress and the important information might be obtained from relationships between stress, corticotropin-releasing hormone (CRH) and symptoms ( 7 ). CRH signaling pathways have been shown to have an important role in stress-related alterations of gut function related to intestinal symptoms ( 7 ). Braak et al. ( 8 ) have attempted to clarify IBS pathophysiology using these strategies.Mast cells are well known to modulate gastrointestinal pathophysiology and are considered to be involved in IBS ( 9 ). Increased numbers of mast cells have been reported in the terminal ileum in patients with IBS, although there was lack of correlation with diarrhea-predominant IBS symptoms ( 4 ). Braak et al. ( 8 ) conclude that the number of mast cells, macrophages (CD68), T cells (CD3 and CD8), and λ FLC-positive mast cells is decreased in IBS patients compared with healthy volunteers. As a general statement, this needs clarifi cation. Th ey note the decrease in the descending colon, but no change was seen in the ascending colon and immune cell numbers in the small intestine were not measured. Furthermore, mast cells in the gut musculature ( ...

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

“…17,18 However, others suggested there was no significant change in MCs density in IBS. [19][20][21] Further data confirmed the hypothesis that the function but not numbers of the mast cell is more valuable to be assessed, 22 since the presence of MCs per se does not necessarily imply they are pathogenic unless they are activated. 17 Although no difference in the number of MCs was observed in IBS, the degranulation or activation rate of MCs was significantly higher, 19 the mucosal content and spontaneous release of tryptase and histamine were increased in IBS subjects.…”

Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells

“…MCs and their mediators have been implicated in neuropsychiatric diseases , IC/BPS (Sant et al, 2007), and irritable bowel syndrome (Theoharides et al, 2012b). Increased number of activated MCs was also reported in skin biopsies of FMS patients (Blanco et al, 2010).…”

“…Moreover, chronic urticaria, which involves MCs, has been identified in some FMS patients (Torresani et al, 2009). However, the numbers of MCs may not be as important as the degree of their activation or the specific mediators that they secrete (Theoharides et al, 2012b).…”

Mast Cells in Irritable Bowel Syndrome and Ulcerative Colitis: Function Not Numbers Is What Makes All the Difference

“…All publications to date, including the one by Choi et al [3], did not report MC activation, which, according to some, is more important than actual numbers [4].…”