Novel synthetic retinoic acid inhibits rat collagen arthritis and differentially affects serum immunoglobulin subclass levels.
Retinoids affect many biological processes such as cell proliferation, differentiation and morphogenesis, but their effects on arthritic patients and animal models of arthritis are controversial. We tested the effect of a novel synthetic retinoic acid, Am-80 (4-[(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid), on type-II collagen (CII)-induced arthritis (CIA) in rats. Am-80 markedly suppressed the incidence of arthritis, hindpaw swelling and bone destruction. In contrast, 13-cis-retinoic acid (13-cis-RA) hardly inhibited these CIA symptoms. Moreover, Am-80, but not 13-cis-RA, strongly reduced the serum level of anti-CII antibody and differentially affected the levels of immunoglobulin (Ig) subclasses in vivo: IgG1 and IgG2a levels were decreased, while IgA level was increased without any change in the IgM level. These findings indicate that Am-80 may be one of the lead retinoic acids of a new class of anti-inflammatory agents.
Discovery Research Laboratories II, Shionogi and Co., Osaka, Japan.
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Kuwabara
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Shudo
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Y
Hori
D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D001565:Benzoates / Q000627:therapeutic use*; D003094:Collagen / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000097:blood*; D051381:Rats; D011917:Rats, Inbred Lew; D012176:Retinoids / Q000627:therapeutic use*; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*
D018501:Antirheumatic Agents; D001565:Benzoates; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D012176:Retinoids; D013764:Tetrahydronaphthalenes; C061133:tamibarotene; D003094:Collagen