The effects of nonsteroidal anti-inflammatory 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 inhibition of prostaglandin (PG) synthesis. However, effects of NSAIDs on immune responses are not fully understood. This study investigated effects of indomethacin and a new NSAID (d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid, termed as M-5011 in this study) on cytokine production, lymphocyte proliferation, activities of natural killer (NK) and lymphokine 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 phytohemagglutinin (PHA)-stimulated PBMC and enhanced NK and LAK cell activities. In contrast, indomethacin was more potent than M-5011 in inhibition of both PG synthesis and Ig secretions by pokeweed mitogen (PWM)-stimulated PBMC. 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.
Tanaka
K
K
Division of Immunopharmacology, Hikone Research Laboratory, Maruho Co. Ltd., Shiga, Japan.
Tanaka
H
H
Kanemoto
Y
Y
Tsuboi
I
I
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000187:drug effects*; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D010666:Phenylpropionates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D010666:Phenylpropionates; C104139:2-(4-(3-methyl-2-thienyl)phenyl)propionic acid; D015232:Dinoprostone; D007213:Indomethacin