Possible background mechanisms of the effectiveness of cyclooxygenase-2 inhibitors in the treatment of rheumatoid arthritis.
Cyclooxygenase (COX)-2 was induced in an acute exudative inflammatory model (rat carrageenin-induced pleurisy) in which prostaglandin E2, 6-keto-prostaglandin F1alpha, and thromboxane B2 were generated in the pleural fluid. Selective COX-2 inhibitors, such as NS-398, inhibited the plasma exudation and generation of prostaglandin E2, but not that of thromboxane B2 and 6-keto-prostaglandin F1alpha, in the pleural fluid. In proliferative inflammatory models, COX-2 was induced, and selective COX-2 inhibitors suppressed granuloma formation, particularly, microvessel formation. COX-2 was induced during angiogenesis in a sponge model implanted into skin of rat, and the COX-2 inhibitor suppressed the angiogenesis. As induction of COX-2 was reported in osteoblasts, COX-2 was involved in most characteristic responses of acute exudative inflammation, granuloma formation, bone resorption, and pain in rheumatoid arthritis. The prevention of these COX-2 responses provides a rationale for the effectiveness of COX-2 inhibitors in the treatment of rheumatoid arthritis.
Katori
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan. hy3m-ktr@asahi-net.or.jp
Majima
M
M
Harada
Y
Y
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002351:Carrageenan; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic / Q000201:enzymology; D010996:Pleural Effusion / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D013276:Stomach Ulcer / Q000201:enzymology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D002351:Carrageenan; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases