Suppressive effects of rebamipide, a novel anti-ulcer agent, on the number and function of granulocytes and extrathymic T cells in mice

Rebamipide, established as a therapeutic drug for gastritis and gastric ulcers, was examined as to how leukocytes and lymphocyte subsets are modulated in mice by its administration. Rebamipide is known to act as a prostaglandin inducer and a scavenger of free radicals and superoxides. When rebamipide was orally administered every day for one week (1 mg/day/mouse), the numbers of granulocytes and extrathymic T cells tended to decrease, especially in the liver and bone marrow. Experiments were then extended to mice loaded with elevated levels of granulocytes and extrathymic T cells in various organs due to the injection of ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID). The elevation in the number and function of granulocytes and extrathymic T cells, normally induced by such administration, was suppressed by subsequent oral administrations of rebamipide. The function of granulocytes was estimated by the expression of iNOS mRNA and the Ca2+ influx in response to bacterial stimuli, whereas that of extrathymic T cells was judged based on cytotoxic function against syngeneic thymocytes. Rebamipide suppressed the number and function of both granulocytes and extathymic T cells in various organs. Since granulocytes and extrathymic T cells have the ability to induce tissue damage, the present results might be highly illustrative of the underlying mechanisms of this drug in the prevention of mucosal tissue damage.