A Novel Macrolide Solithromycin Exerts Superior Anti-inflammatory Effect via NF-κB Inhibition

• DOI: 10.1124/jpet.112.200733
• Publication Date: 2013-01-29T11:16:02Z
• Authors: Yoshiki Kobayashi; Hiroo Wada; Christos Rossios; Dai Takagi; Manabu Higaki; Shin'ichiro Mikura; Hajime Goto; Peter J. Barnes; Kazuhiro Ito
• Keywords: Interleukin 8; Diffuse panbronchiolitis

Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease, such as obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro vivo. However the efficacies current macrolides relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior clinical use. The (SOL) on lipopolysaccharide-induced TNF<i>α</i> (tumor necrosis factor <i>α</i>) and/or CXCL8 (C-X-C motif chemokine ligand 8; interleukin-8) release, phorbol 12-myristate 13-acetate-induced MMP9 (matrix metalloproteinase 9) activity NF-<i>κ</i>B (nuclear factor-<i>κ</i>B) under conditions oxidative stress have been evaluated compared with erythromycin, clarithromycin, azithromycin, telithromycin macrophage-like PMA-differentiated U937 cells peripheral blood mononuclear (PBMC) obtained from COPD patients. We examined effect SOL cigarette smoke-induced airway inflammation mice. exerted inhibitory TNF<i>α</i>/CXCL8 production monocytic cells. In addition, suppressed release PBMC patients at 10 <i>µ</i>M, which is times more potent than other tested. Activated by was completely reversed SOL. inhibited neutrophilia pro-MMP9 vivo, although erythromycin did not inhibit them. Thus, better profiles currently used clinic may be promising antimicrobial macrolide for treatment future.