title: Ephedrine hydrochloride protects mice from LPS challenge by promoting IL-10 secretion and inhibiting proinflammatory cytokines.
abstract: 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 α- and β-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-α (TNFα) 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.
authors.affiliation: Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yuejuan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Guo
authors.forename: Weigang
authors.initials: W
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Li
authors.forename: Aoxiang
authors.initials: A
authors.lastname: Zheng
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jinzhu
authors.initials: J
authors.lastname: Ma
authors.forename: Mingyue
authors.initials: M
authors.lastname: Wen
authors.forename: Muyi
authors.initials: M
authors.lastname: Yang
authors.forename: Huazhang
authors.initials: H
authors.lastname: An
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D054426:Chemokine CXCL2 / Q000037:antagonists & inhibitors / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004809:Ephedrine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D018805:Sepsis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D054426:Chemokine CXCL2; D004809:Ephedrine; D016753:Interleukin-10; D018664:Interleukin-12; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C404915:Cxcl2 protein, mouse; C556062:IL10 protein, mouse