SUPPRESSIVE EFFECTS OF REBAMIPIDE, A NOVEL ANTIULCER AGENT, ON THE NUMBER AND FUNCTION OF GRANULOCYTES AND EXTRATHYMIC T-CELLS IN MICE

Rebamipide, established as a therapeutic drug for gastritis and gastri c ulcers, was examined as to how leukocytes and lymphocyte subsets are modulated in mice by its administration. Rebamipide is known to act a s a prostaglandin inducer and a scavenger of free radicals and superox ides. When rebamipide was orally administered every day for one week ( 1 mg/day/mouse), the numbers of granulocytes and extrathymic T cells t ended to decrease, especially in the liver and bone marrow. Experiment s were then extended to mice loaded with elevated levels of granulocyt es and extrathymic T cells in various organs due to the injection of k etoprofen, a nonsteroidal anti-inflammatory drug (NSAID). The elevatio n 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 e stimated by the expression of iNOS mRNA and the Ca2+ influx in respons e 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 b e highly illustrative of the underlying mechanisms of this drug in the prevention of mucosal tissue damage.