title: Ciclamilast ameliorates adjuvant-induced arthritis in a rat model.
abstract: We assessed the effect of a novel and selective phosphodiesterase 4 (PDE4) inhibitor, ciclamilast, on chronic inflammation in adjuvant-induced arthritis (AIA), a rat model of rheumatoid arthritis (RA), and acute inflammation in the rat and mouse model of carrageenan-induced paw edema and peritonitis. Our results showed that daily oral administration of ciclamilast at 1, 3, and 10 mg/kg dose-dependently inhibited the increase in hind paw volume of rats with AIA. The inhibition of paw edema was associated with inhibition of both the production of cytokines such as TNF-α, IL-1β, and IL-6 and cell infiltration assessed in subcutaneous paw tissue. Moreover, there was significantly less tissue destruction in the ciclamilast-treated rats compared to the vehicle-treated rats, as assessed by radiographic analysis and histopathological evaluation. In the two acute inflammation models, ciclamilast inhibited carrageenan-induced paw edema in rats and inflammatory cell migration into the peritoneal cavity in mice in a dose-dependent manner. These results not only suggest that ciclamilast, as a disease-modifying antirheumatic drug (DMARD), can attenuate RA but also provide proof of principle that a PDE4 inhibitor may be useful for the treatment of arthritis.
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou 310053, China.
authors.forename: Zhi-cheng
authors.initials: ZC
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou 310053, China.
authors.forename: Shui-juan
authors.initials: SJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Zhejiang University School of Medicine, No. 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, Zhejiang University School of Medicine, No. 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Zhejiang University School of Medicine, No. 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Xin-fu
authors.initials: XF
authors.lastname: Yang
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou 310053, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, Zhejiang University School of Medicine, No. 866 Yuhangtang Road, Hangzhou 310058, China ; Laboratory Animal Center of Zhejiang University, Hangzhou 310058, China.
authors.forename: Qiang-min
authors.initials: QM
authors.lastname: Xie
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002351:Carrageenan; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D010538:Peritonitis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D011859:Radiography; D017207:Rats, Sprague-Dawley; D040521:Subcutaneous Tissue / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D001549:Benzamides; D016207:Cytokines; C515489:N-(3,5-dichloro-4-pyrid-4-yl)-3-cyclopentyl-oxy-4-methylbenzamide; D011725:Pyridines; D002351:Carrageenan