Anti-inflammatorische Eigenschaften von Makrolid-Antibiotika bei akuter Lipopolysaccharid-induzierter Entzündung
Macrolides are a well-established class of antibacterial agents being particularly effective for respiratory tract infections. In addition, macrolides have beneficial clinical effects in the treatment of diffuse panbronchiolitis (DPB), a chronic inflammatory airway disease with predominant incidence in Japan. In this regard, it has been suggested that the anti-inflammatory action, but not the antimicrobial activity of macrolides, is responsible for the effectiveness of these compounds. In the
... compounds. In the present study, the anti-inflammatory activitiy of macrolide antibiotics was investigated in vivo and in vitro. In a model of acute lung inflammation, caused by nasal administration of lipopolysaccharide (LPS), the mRNA- and protein expression of proinflammatory cytokines such as TNF alpha, IL-1 beta, IL-6 and IFN gamma was attenuated after pretreatment of mice with roxithromycin or telithromycin. Using a model of acute systemic inflammation, caused by intraperitoneal injection of LPS, similar observations were found in other organs such as liver, heart and kidney. Pretreatment of mice with roxithromycin or telithromycin attenuated the LPS-induced mRNA- and protein expression of TNF alpha, IFN gamma and in part IL-1 beta. Furthermore, due to the reduced production of cytokines the increase of inducible nitric oxide synthase (NOS-II) and the formation of its product nitric oxide (NO) were clearly diminished by pretreatment with roxithromycin or telithromycin. In addition, in vitro studies with macrophages were conducted to characterize the molecular mechanism of the anti-inflammatory properties of macrolides. The results suggest that macrolides suppress the LPS-induced production of proinflammatory cytokines by inhibition of the activation of mitogen-activated protein kinases (MAPK).