THE EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON IMMUNE FUNCTIONS OF HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

It is generally accepted that the nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit anti-inflammatory effects primarily through inhibiti on of prostaglandin (PG) synthesis. However, effects of NSAIDs on immu ne responses are not fully understood. This study investigated effects of indomethacin and a new NSAID (d-2-[4-(3-methyl-2-thienyl)phenyl]pr opionic acid, termed as M-5011 in this study) on cytokine production, lymphocyte proliferation, activities of natural killer (NK) and lympho kine activated killer (LAK) cells and secretion of immunoglobulin (Ig) . Both indomethacin and M-5011 augmented interleukin (IL)-2 production , whereas they suppressed IL-6 production both at the protein and mRNA levels. These two NSAIDs augmented proliferation of phytohemagglutini n (PHA)-stimulated PBMC and enhanced Mt and LAK cell activities. In co ntrast, indomethacin was more potent than M-5011 in inhibition of both PG synthesis and Ig secretions by pokeweed mitogen (PWM)-stimulated P BMC. These results suggest that these two NSAIDs equally augment cell- mediated immunity, whereas indomethacin was more potent than M-5011 in the inhibition of humoral immunity and PG synthesis. (C) 1998 Elsevie r Science B.V. All rights reserved.