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

Abstract

We evaluated the effects of a new non-steroidal anti-inflammatory drug (NSAID), d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), and indomethacin on the production of arachidonate metabolites and pro-inflammatory cytokines in male Sprague-Dawley rats with monosodium urate crystal (MSU)-induced pleurisy. Levels of tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6 in the pleural exudate were determined by biological assays, while prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and cytokine-induced chemoattractant-1 (CINC-1) levels were quantified by enzyme immunoassays. Orally administered M-5011 (5 mg/kg) decreased the pleural exudate volume at 3 and 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 PGE2 in the exudate without affecting LTB4 levels. Increased productions of both IL-6 and CINC-1 in the exudate were reduced by pretreatment with M-5011 or indomethacin, and TNF levels in the exudate were increased by pretreatment of these drugs. Thus, 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 infiltration in rats with MSU-induced pleurisy.

• Authors: N Murakami, S Aihara, K Iwata, T Saito, T Naruse
• Journal: Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 79 Issue 4 Pg. 439-46 (Apr 1999) ISSN: 0021-5198 [Print] Japan
• PMID: 10361883 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• Phenylpropionates
• Leukotriene B4
• Uric Acid
• 2-(4-(3-methyl-2-thienyl)phenyl)propionic acid
• Dinoprostone
• Indomethacin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Cell Line
• Cytokines (drug effects, metabolism)
• Dinoprostone (metabolism)
• Exudates and Transudates (drug effects, metabolism)
• Humans
• Indomethacin (pharmacology)
• Leukotriene B4 (metabolism)
• Male
• Phenylpropionates (pharmacology)
• Pleura (drug effects, metabolism, pathology)
• Pleural Effusion (metabolism)
• Pleurisy (chemically induced, metabolism)
• Rats
• Rats, Sprague-Dawley
• Uric Acid (adverse effects)