Mast cells, inflammation and the neurons 

Mast cells and their chemicals have the potential to mediate the effects of inflammation on enteric nerves because they function as intermediaries between neurons and the inflammatory soup in their environment. Both mast cells and neurons can be increased or decreased by an inflammatory environment and, upon activation, release mediators that can act on the gut neuromuscular apparatus.

Although mast cells are most widely known for their role in allergic responses, these cells are normally present throughout the gut and are involved in a range of physiological and pathological activities including mucosal defense mechanisms and inflammation.

Enteric mastcells and mediators

Enteric mast cells are concentrated with granules that serve as sites of storage for a wide mix of preformed chemical mediators. Antigens stimulate the mast cells to release mediators, which then diffuse into the extracellular space to influence other cell types.

Mast cells may release an array of inflammatory mediators, which may stimulate the residential macrophages on the one hand and intrinsic and extrinsic neurons, on the other hand, which may ultimately result in GI dysfunction and symptoms.

Role of mast cells in inflammatory bowel disorders

There is considerable clinical evidence for mast cell involvement in human IBD. In the colorectal mucosa from patients with CD and UC, the amount of mast cell tryptase is significantly increased as is the number of mast cells in the lamina propria and submucosa.

Increased numbers of mast cells found in the colonic mucosa of IBD patients are accompanied by dramatically increased expression of TNF-alpha, IL-16, and SP. Evidence of mast cell degranulation is found in the intestinal wall of IBD patients, suggesting that mast cell degranulation is involved in the pathogenesis of IBD.

Mast cells mediators include a number of proinflammatory substances (tryptase, histamine, platelet activating factor, prostaglandins, leukotrienes) and have the capacity to produce a variety of cytokines. Mast cells undergo degranulation during intestinal manipulation and may be part of the mechanisms responsible for triggering cellular infiltration and subsequent altered bowel motility.

Several mast cell-derived mediators have neuropharmacological actions on the electrical and synaptic behavior of neurons in the ENS including histamine, interleukin-6, leukotrienes, 5-HT, platelet activating factor, mast cell proteases, adenosine, interleukin-1β, and prostaglandins.

All these mediators lead to irritation of fibroblasts, glia en neurons and creates pain and chronic inflammation.

Mast cells, inflammation, glia and neuronal wind up and the therapeutic role of Normast 

In general, inflammation-related changes in GI function likely involve neurodegeneration and neuroplasticity in the ENS, as well as changes in the structure and function of enteric glia.

Although the mechanisms involved in modulation of enteric neural activity during inflammation are not completely understood, oxidative stress appears to play an important role in the process.

Thus, it is possible that neuroprotective agents that curtail oxidative stress in the ENS could restore gut function and could have utility in the treatment of gut dysfunction in IBD. 

New therapeutic tool for IBD with the body-own endocannabinoid Normast  

Therefore, a mast-cell stabilizor such as Normast, with a combined effect on neurons and glia, as well as on the mast cells, via its effect via the nuclear receptor PPAR, can be a significant new agent in the treatment of IBD. Our clinical observations support this use, and, as Normast is a supplement with clear safety and efficacy data, as well as a host of pharmacological data, it seems compound worthwhile to consider in the treatment of IBD.

 Jan M. Keppel Hesselink, MD, PhD, april 2011