Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease

Abstract

Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and increased gut permeability and may be responsible for some of the symptoms and signs of inflammatory bowel disease. We have used a novel monoclonal antibody (AAI) against tryptase expressed exclusively in the granules of mast cells to enumerate mast cells in rectal biopsies in order to study the effect of inflammatory bowel disease and drug treatment upon rectal mast cell numbers. Rectal mast cell numbers are significantly reduced in inflammatory bowel disease patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control patients (10.1, P less than 0.001) and inflammatory bowel disease patients not taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The reduction in mast cell counts was independent of the degree of inflammation or architectural distortion. There was a negative correlation between the dose of corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank correlation), and the mast cell count was reduced within a few days of treatment and remained low throughout steroid therapy. Mucosal mast cell depletion may be an important mechanism of action of corticosteroids in inflammatory bowel disease.

Mast cell changes in experimental diabetes: focus on attenuation of allergic events

“…The reduction of mast cell number and reactivity as well as of antigen-induced IgE formation, noted in alloxan diabetes, was reversed by surgical bilateral adrenalectomy and by treatment with the steroid blocker RU 486 (Diaz et al 2001, indicating a causative link between the negative regulation of mast cell-IgE system and enhanced serum glucocorticoid levels. These findings were consistent with previous reports which had demonstrated the effect of glucocorticoids in inducing depletion of mast cells in different body sites including skin, lung, and intestine (Pipkorn et al 1989, Goldsmith et al 1990, Finotto et al 1997. Glucocorticoids were shown to have their anti-inflammatory activity due to inhibition of gene transcription, resulting in a smaller production of a wide range of effectors such as cytokines (Schleimer 1993, Barnes 2004, including the stem cell factor (SCF) (Finotto et al 1997), IL-3 andIL-4 (Braun et al 1997).…”

Dexamethasone prevents visceral hyperalgesia but not colonic permeability increase induced by luminal protease-activated receptor-2 agonist in rats

“…22 Corticosteroid treatment reduces mast cell number in rectal biopsy specimens of patients with IBD; however, the reduction in mast cell counts is independent of the degree of inflammation. 23 Budesonide and dexamethasone had potent inhibitory effects on the release of cytokines from a human mast cell line 24 ; however, in another study, dexamethasone treatment failed to inhibit the release of mast cell mediators from cultures of human airway, skin and intestinal tissues. 25 In our study, we show that a 4-day daily treatment with dexamethasone inhibits PAR-2 agonist-induced rectal hyperalgesia in rats.…”

Key role of mast cells and their major secretory products in inflammatory bowel disease

“…Thus the beneficial effects of 5-aminosalicylic acid on IBD were at least partially due to its mast cell stabilizing activity. Similarly, the effective treatment of IBD by corticosteroids might also be partially associated with its action on mast cells as significantly reduced numbers of mast cells were observed in the colon throughout steroid therapy [176] . The ineffective treatment of ulcerative colitis by mast cell stabilizer, cromolyn sodium [177] was most likely due to the drug that did not affect release of histamine from colon mast cells [178] .…”