期刊
BIOMED RESEARCH INTERNATIONAL
卷 2015, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2015/786104
关键词
-
资金
- National Science Foundation of China [81373224]
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 10mg/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-alpha, IL-1 beta, 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.
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