EFFECT OF THE NOVEL RADICAL SCAVENGER AD0261 ON LYMPHOCYTE-ACTIVATION

A recent investigation has indicated that reactive oxygen species (ROS ) may play an important role in the activation of lymphocytes. The mai n aim of the present study is to find out what effect on lymphocyte ac tivation is attributable to radical scavengers (RSs). AD0261 (AD) is a novel RS which displays strong inhibitory action on the generation of lipid peroxides and superoxide anions. This compound has been shown t o be effective in inhibiting tritiated thymidine ([3H]TdR) incorporati on into, IL-2 release from and IL-2 receptor (Rc) expression on Con A- stimulated mouse spleen cells and PHA-P-stimulated lymphocytes of huma n peripheral blood, IC50 values being in the range 1-10 mu M. It also inhibited erythema formation elicited by transferring PHA-P-stimulated lymphocytes into guinea pigs (30-40% inhibition at 10 mu M, p<0.05). Further study showed that the activity of ornithine decarboxylase (ODC ), which is a critical enzyme for cell proliferation, was inhibited by AD in a dose-dependent manner (IC50 = 1.0 mu M). In summary, AD would seem to affect the lymphocyte activation by inhibiting ODC activity, probably through the action of ROS trapping.