Sepsis and its derivative endotoxic shock are still serious conditions with high mortality in the intensive care unit. The mechanisms that ensure the balance of proinflammatory cytokines and anti-inflammatory cytokine production are of particular importance. As an active alpha- and beta-adrenergic agonist, ephedrine hydrochloride (EH) is a widely used agent for cardiovascular diseases, especially boosting blood pressure. Here we demonstrate that EH increased Toll-like receptor 4 (TLR4)-mediated production of interleukin 10 (IL-10) through p38 MAPK activation. Simultaneously, EH negatively regulated the production of proinflammatory cytokines. Consistently. EH increased lipopolysaccharide (LPS)-induced serum IL-10 and inhibited tumor necrotic factor-a (TNF alpha) production in vivo. As a result, EH treatment protected mice from endotoxic shock by lethal LPS challenge. In brief, our data demonstrated that EH could contribute to immune homeostasis by balancing the production of proinflammatory cytokines and anti-inflammatory cytokine in TLR4 signaling. This study provides a potential usage of EH in autoimmunologic diseases or other severe inflammations. (C) 2012 Elsevier B.V. All rights reserved.
[1]Shanghai Univ Tradit Chinese Med, Dept Immunol & Microbiol, Shanghai 201203, Peoples R China.
[2]Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China.
[3]Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China.
[4]Hutchison MediPharma Ltd, Shanghai 201203, Peoples R China.
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