Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease such as chronic obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro and in vivo. However the anti-inflammatory efficacies of current macrolides are relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior anti-inflammatory effects to macrolides in current clinical use. The effects of solithromycin (SOL) on LPS-induced TNFα and/or CXCL8 release, PMA-induced MMP9 activity and NF-κB activity under conditions of oxidative stress have been evaluated and compared with the effects of erythromycin, clarithromycin and azithromycin in human monocytic U937 cells and peripheral blood mononuclear cells (PBMC) obtained from COPD patients. We also examined effect of SOL on cigarette smoke-induced airway inflammation in mice. SOL exerted superior inhibitory effects on TNFα/CXCL8 production and MMP9 activity in U937 cells. In addition, SOL suppressed TNFα release and MMP9 activity in PBMC from COPD patients at 10µM, which is 100 times more potent than the other macrolides tested. Activated NF-κB due to oxidative stress was completely reversed by SOL. SOL also inhibited cigarette smoke-induced neutrophilia in vivo. Thus, SOL showed better anti-inflammatory profiles compared with macrolides currently used in the clinic, and may be a promising anti-inflammatory and anti-microbial macrolide for the treatment of COPD in the future.
- anti-inflammatory drugs
- lung inflammation
- pulmonary inflammation
- pulmonary pharmacology
- Received September 28, 2012.
- Revision received December 20, 2012.
- Accepted December 20, 2012.
- The American Society for Pharmacology and Experimental Therapeutics