Effect of a novel non-steroidal anti-inflammatory drug (M-5011) on cytokine levels in rats with monosodium urate crystal-induced pleurisy

We evaluated the effects of a new non-steroidal anti-inflammatory drug (NSA ID), d-2-[4-(3-methy;-2-thienyl)phenyl]propionic acid (M-5011), and indomet hacin on the production of arachidonate metabolites and pro-inflammatory cy tokines in male Sprague-Dawly rats with monosodium urate crystal (MSU)-indu ced pleurisy. Levels of tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6 in the pleural exudate were determined by biological assays, while pr ostaglandin E-2 (PGE(2)), leukotriene B-4 (LTB4) and cytokine-induced chemo attractant-1 (CINC-1) levels were quantified by enzyme immunoassays. Orally administered M-5011 (5 mg/kg) decreased the pleural exudate volume at 3 an d 4 hr after MSU injection. Indomethacin (10 mg/kg) decreased the volume at 3-5 hr. These drugs reduced the number of leukocytes in the pleural cavity at 6 hr. Both NSAIDs also reduced the content of PGE(2) in the exudate wit hout affecting LTB4 levels. Increased productions of both IL-6 and CINC-1 i n the exudate were reduced by pretreatment with M-5011 or indomethacin, and TNF levels in the exudate were increased by pretreatment of these drugs. T hus, M-5011 inhibits the production of both IL-6 and CINC-1 at lower doses than those of indomethacin, and the inhibitory effect of M-5011 on CINC-1, but not IL-6, may partly contribute to the inhibition of leukocyte infiltra tion in rats with MSU-induced pleurisy.