Suppression of the acute inflammatory response of porcine alveolar- and liver macrophages

During infection and inflammation drug disposition and hepatic metabolism a re markedly affected in mammals. Pro-inflammatory mediators play an importa nt role in the suppression of (cytochrome-P450-mediated) drug metabolism. I nflammatory mediators like cytokines, nitric oxide (NO), reactive oxygen sp ecies (ROS) and eicosanoids are released by activated macrophages from vari ous sources, including liver and lung, It was the aim of this study to investigate ways to suppress the activation of macrophages during the onset of the inflammatory cascade. Therefore por cine lung and liver macrophages were isolated, and incubated with lipopolys accharide (LPS) to initiate an acute inflammatory response, represented by the release of high amounts of tumour necrosis factor-alpha (TNF-alpha) int o the culture medium. Additionally the primary macrophages were coincubated with phosphodiesterase-IV (PDE-TV)-inhibitors or beta-adrenoceptor agonist s that in previous studies demonstrated strong suppressive effects on TNF-a lpha release. Especially the beta-adrenoceptor agonists showed to be very p otent TNF-alpha suppressants, which indicates that the beta-adrenoceptor mi ght be an interesting target for suppression of activation of macrophages, This was strengthened by the observation that the beta-adrenoceptor express ion was not altered during the onset of the inflammatory cascade.