Abstract

Background & Aims: The pathogenesis of Clostridium difficile toxin A–induced intestinal inflammation is not completely understood. The aim of this study was to define the contribution of mast cells to the fluid secretion and neutrophil infiltration associated with toxin A–induced enteritis. Methods: Fluid secretion and neutrophil infiltration in toxin A– or buffer–challenged ileal loops were assessed in normal, mast cell–deficient, and mast cell–deficient Kit W/Kit W-v mice that had undergone selective repair of their mast cell deficiency. The effect of a specific substance P–receptor antagonist was also studied. Results: Intestinal fluid secretion and neutrophil recruitment were significantly diminished in mast cell–deficient Kit W/Kit W-v and mast cell–deficient Mgf Sl/Mgf Sl-d mice compared with the respective normal mice. Mast cell–reconstituted Kit W/Kit W-v mice showed responses similar to the normal congenic mice. Administration of a specific substance P–receptor antagonist (CP-96,345) reduced toxin A–induced intestinal fluid secretion and inhibited neutrophil infiltration in normal, mast cell–deficient Kit W/Kit W-v , and mast cell–reconstituted Kit W/Kit W-v mice. Conclusions: C. difficile toxin A elicits intestinal fluid secretion and neutrophil infiltration by both mast cell–dependent and –independent pathways, and substance P participates in both pathways. GASTROENTEROLOGY 1998;114:956-964

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