The augmentation of lymphokine-activated killer cell activity by indomethacin in vitro is not mediated by prostaglandin E2 suppression.

The effects of three nonsteroidal antiinflammatory drugs (NSAIDs), namely, indomethacin, aspirin, and mefenamate (ponstan), on the lymphokine-activated killer (LAK) cell activities generated from coculturing recombinant interleukin-2 (rIL-2) and normal human peripheral blood mononuclear cells (PBMCs) for 3 to 4 days were investigated. The LAK cell activities were measured by a 4 hour 51Cr release microcytotoxicity assay using HL-60 and K-562 as target cells. Indomethacin was found to have significant augmenting effect on LAK cell activity at the concentration of 5 x 10(-5) M, whereas aspirin and ponstan did not show the same effect at the same concentration. Additional experiments, however, demonstrated that all of these 3 agents could effectively suppress the production of prostaglandin E2 (PGE2) in the culture medium. These results indicated that PGE2 suppression may not be the only mechanism of indomethacin for upregulation of LAK cell activity, and even immune functions.