Simmons16 (1961) was the first to suggest mast cells as a cause of IC. Mast cells contain cytoplasmic granules, which in turn contain substances such as histamine, leukotrienes, prostaglandins, and tryptases. All these substances are capable of stimulating inflammation. Degranulation or activation of mast cells can occur as a part of an immunoglobulin E-mediated hypersensitivity reaction or in response to multiple other stimuli including neuro-transmitters substance P, cytokines, anaphylatoxins (complement: C3a, 4a, 5a), bacterial toxins, and stress.17,18 Mastocytosis has been reported in the bladders of 30% to 65% of patients with IC.19,20 Increased substance P-containing fibers were found adjacent to mast cells in the bladder biopsies of IC patients.21 Elevated levels of histamine and its metabolites, in the urine of IC patients, were reported by some investigators. Others found overlap or no difference in urinary histamine excretions in IC patients and controls.22,23 Whether mast cells have a primary or secondary role in the etiology of IC is not exactly known.
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