tailieunhanh - Báo cáo y học: "Phosphodiesterase 4 inhibition but not beta-adrenergic stimulation suppresses tumor necrosis factor-alpha release in peripheral blood mononuclear cells in septic shock"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Phosphodiesterase 4 inhibition but not beta-adrenergic stimulation suppresses tumor necrosis factor-alpha release in peripheral blood mononuclear cells in septic shock. | Available online http content 1 2 6 R159 Open Access Research Phosphodiesterase 4 inhibition but not beta-adrenergic stimulation suppresses tumor necrosis factor-alpha release in peripheral blood mononuclear cells in septic shock Andreas Link Simina Selejan Christoph Maack Monika Lenz and Michael Bohm Klinik fur Innere Medizin III Universitat des Saarlandes 66421 Homburg Saar Germany Corresponding author Andreas Link link@ Received 22 Sep 2008 Revisions requested 20 Oct 2008 Revisions received 19 Nov 2008 Accepted 17 Dec 2008 Published 17 Dec 2008 Critical Care 2008 12 R159 doi cc7158 This article is online at http content 12 6 R159 2008 Link et al. licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Introduction Stimulation of beta-adrenergic receptors p2-ARs inhibits tumor necrosis factor-alpha TNF-a release in monocytes. In septic shock endogenous catecholamines induce P2-AR downregulation leading to an increased TNF-a release. The aims of this study were to analyze the molecular mechanisms of p-adrenergic downregulation and to explore therapeutic interventions with maintained anti-inflammatory efficacy in septic shock using the inhibition of phosphodiesterase 4 PDE4 . Methods We conducted in vitro stimulation of peripheral blood mononuclear cells of healthy volunteers n 20 and patients with septic shock n 20 with lipopolysaccharide LPS or Staphylococcus aureus enterotoxin B SEB without or with isoprenaline forskolin an activator of adenylate cyclase or ropipram an inhibitor of PDE4 . We also conducted flow cytometric analysis of Toll-like receptor TLR 4 and TLR2 surface expression and intracellular TNF-a production of untreated and stimulated CD14 monocytes. .