Mechanisms involved in enteropathy induced by administration of nonsteroidal antiinflammatory drugs (NSAIDS)

Mice received oral indomethacin (1 mg/mouse) daily for five days. It was fo und that severe gastroenteropathy (ie, paralytic stomach and necrotic intes tine) was induced on the sixth day. Ulcer formation was also seen at many s ites in the digestive tract, especially in the colon. In parallel with the increase in the number of leukocytes in the digestive tract, the proportion of granulocytes increased at various sites, for example, in the intraepith elium and lamina propria of the colon and the lamina propria of the appendi x. The number of extrathymic T cells at these sites in the digestive tract, especially gamma delta T cells in the colon, increased. A functional assay revealed that granulocytes isolated from mice injected with indomethacin w ere activated in terms of their superoxide production upon stimulation. In conjunction with the data on the simultaneous activation of granulocytes in the liver and blood, the present results suggest that nonsteroidal antiinf lammatory drugs (NSAIDs) have the potential to induce severe granulocytosis in specific sites of the body, possibly via their stimulatory effect on th e sympathetic nervous system (ie, granulocytes bear adrenergic receptors on their surface).