摘要
Approaches for controlling inflammatory responses and reducing the mortality rate of septic patients remain clinically ineffective; new drugs need to be identified that can induce anti-inflammatory responses. Ephedrine hydrochloride （EH） is a compound that is widely used in cardiovascular diseases, especially to treat hypotension caused by either anesthesia or overdose of antihypertensive drugs. In this study, we reported that EH also plays an important role in the control of the inflammatory response. EH increased IL-IO and decreased proinflammatory cytokine （IL-6, tumor-necrosis factor （TNF）-a, IL-12 and IL-11~） expression in primary peritoneal macrophages and Raw264.7 cells treated with peptidoglycan （PGN）, a Gram-positive cell wall component. The anti-inflammatory role of EH was also demonstrated in an experimental mouse model of peritonitis induced by intraperitoneal PGN injection. The phosphatidylinositol 3-kinase （PI3K）/Akt pathway was found to be responsible for the EH-mediated increase in IL-IO production and decrease in IL-6 expression. Therefore, our results illustrated that EH can help maintain immune equilibrium and diminish host damage by balancing the production of pro- and anti-inflammatory cytokines after PGN challenge. EH may be a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection.
Approaches for controlling inflammatory responses and reducing the mortality rate of septic patients remain clinically ineffective; new drugs need to be identified that can induce anti-inflammatory responses. Ephedrine hydrochloride （EH） is a compound that is widely used in cardiovascular diseases, especially to treat hypotension caused by either anesthesia or overdose of antihypertensive drugs. In this study, we reported that EH also plays an important role in the control of the inflammatory response. EH increased IL-IO and decreased proinflammatory cytokine （IL-6, tumor-necrosis factor （TNF）-a, IL-12 and IL-11~） expression in primary peritoneal macrophages and Raw264.7 cells treated with peptidoglycan （PGN）, a Gram-positive cell wall component. The anti-inflammatory role of EH was also demonstrated in an experimental mouse model of peritonitis induced by intraperitoneal PGN injection. The phosphatidylinositol 3-kinase （PI3K）/Akt pathway was found to be responsible for the EH-mediated increase in IL-IO production and decrease in IL-6 expression. Therefore, our results illustrated that EH can help maintain immune equilibrium and diminish host damage by balancing the production of pro- and anti-inflammatory cytokines after PGN challenge. EH may be a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection.
基金
This work was supported by grants from the National Key Basic Research Program of China （2010CB529901 and 2010CB530600）, the National Natural Science Foundation of China （31100619 and 30972705）, the China Postdoctoral Science Foundation （20110490186）, the Chen-guang Plan Project of Shanghai Educational Municipal Education Commission （11CG48 and szyl0004）, the Specialized Research Fund for the Doctoral Program of Higher Education （20113107120014） and the Leading Academic Discipline Project of Shanghai Municipal Education Commission （J50301） （Yuejuan Zheng, Shanghai University of T.C.M）.
