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BioMed Research International
Volume 2015 (2015), Article ID 786104, 11 pages
http://dx.doi.org/10.1155/2015/786104
Research Article

Ciclamilast Ameliorates Adjuvant-Induced Arthritis in a Rat Model

1College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou 310053, China
2Department of Pharmacology, Zhejiang University School of Medicine, No. 866 Yuhangtang Road, Hangzhou 310058, China
3Laboratory Animal Center of Zhejiang University, Hangzhou 310058, China

Received 26 July 2014; Revised 23 September 2014; Accepted 25 September 2014

Academic Editor: Monica Fedele

Copyright © 2015 Zhi-cheng Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.