Effects of Nonsteroidal Anti-Inflammatory Drugs on Interleukin-1 Receptor Antagonist Production in Cultured Human Peripheral Blood Mononuclear Cells

• Published in: Prostaglandins 1997-11, Vol.54 (5), p.795-804
• Main Authors: Kusuhara, Hidenobu, Matsuyuki, Hirofumi, Okumoto, Takeki
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Cells, Cultured; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - genetics; Interleukin-1 receptor antagonist; Isoxazoles - pharmacology; Leukocytes, Mononuclear - chemistry; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; mofezolac; mRNA expression; non-steroidal anti-inflammatory drug; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Sialoglycoproteins - blood; Sialoglycoproteins - genetics
• ISSN: 0090-6980
• DOI: 10.1016/S0090-6980(97)00159-7

The effects of nonsteroidal anti-inflammatory drugs (NSAIDs), mofezolac, indomethacin, sodium diclofenac, and zaltoprofen, on the production of interleukin-1 receptor antagonist (IL-1ra) were examined in cultured human peripheral blood mononuclear cells (PBMC). Among the NSAIDs tested, mofezolac and sodium diclofenac were found to stimulate the mRNA expression for IL-1ra without affecting the mRNA expression for IL-1β. These two drugs also stimulated the secretion of IL-1ra by PBMC in the absence of bacterial lipopolysaccharide (LPS), however, the stimulatory effect of sodium diclofenac diminished in the presence of LPS. Mofezolac suppressed the mRNA expression for IL-1β in PBMC stimulated with exogenous IL-1β, indicating the secreted IL-1ra in the presence of mofezolac to be biologically active. Since IL-1ra suppresses the function of IL-1, a pro-inflammatory cytokine, the stimulatory effect of such NSAIDs as mofezolac on IL-1ra production could also be one of the mechanisms involved in its anti-inflammatory and antinociceptive actions.