Effect of a Novel Non-steroidal Anti-inflammatory Drug (M-5011) on Cytokine Levels in Rats With Monosodium Urate Crystal-Induced Pleurisy
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概要
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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-Dawly 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.
- 社団法人 日本薬理学会の論文
- 1999-04-01
著者
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斎藤 徹
Faculty Of Pharmaceutical Sciences Kanazawa University
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Suzuki T
Drug Discovery Research Laboratory Sanwa Kagaku Kenkyusho Co. Ltd.
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Suzuki T
Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University
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Saito T
Research And Development Headquarters Hokurikit Seiyaku Co. Ltd.
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Saito Takako
Research And Development Laboratories Maruho Co. Ltd.
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Suzuki Toshikazu
Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.
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Iwata Kazumi
Research And Development Laboratories Maruho Co. Ltd.
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Naruse Taeko
Department Of Molecular Life Science Tokai University School Of Medicine
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Suzuki T
Research Unit Of Pharmaceutics College Of Pharmacy Nihon University
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Sugihara T
Faculty Of Pharmaceutical Sciences Tokushima Bunri University
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Saito T
Research And Development Laboratories Maruho Co. Ltd.
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Naruse T
Research And Development Laboratories Maruho Co. Ltd.
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NARUSE Tomohiro
Research and Development Laboratories, Maruho Co., Ltd
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Murakami Naofumi
Research And Development Laboratories Maruho Co. Ltd.
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Murakami Naofumi
Research & Development Laboratories Maruho Co. Ltd.
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AIHARA Shizuhiko
Research and Development Laboratories, Maruho Co., Ltd.
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Naruse Tomohiro
Research & Development Laboratories Maruho Co. Ltd.
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Aihara Shizuhiko
Research And Development Laboratories Maruho Co. Ltd.
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