Ephedrine hydrochloride protects mice from LPS challenge by promoting IL-10 secretion and inhibiting proinflammatory cytokines

Yuejuan Zheng; Ziyi Guo; Weigang He; Yang Yang; Yuhu Li; Aoxiang Zheng; Ping Li; Yan Zhang; Jinzhu Ma; Mingyue Wen; Muyi Yang; Huazhang An; Guang Ji; Yizhi Yu

doi:10.1016/j.intimp.2012.03.005

Ephedrine hydrochloride protects mice from LPS challenge by promoting IL-10 secretion and inhibiting proinflammatory cytokines

Int Immunopharmacol. 2012 May;13(1):46-53. doi: 10.1016/j.intimp.2012.03.005. Epub 2012 Mar 22.

Authors

Yuejuan Zheng¹, Ziyi Guo, Weigang He, Yang Yang, Yuhu Li, Aoxiang Zheng, Ping Li, Yan Zhang, Jinzhu Ma, Mingyue Wen, Muyi Yang, Huazhang An, Guang Ji, Yizhi Yu

Affiliation

¹ Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

PMID: 22446503
DOI: 10.1016/j.intimp.2012.03.005

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
Apoptosis / drug effects
Blotting, Western
Cell Culture Techniques
Cell Line
Chemokine CXCL2 / antagonists & inhibitors
Chemokine CXCL2 / blood
Dose-Response Relationship, Drug
Ephedrine / administration & dosage
Ephedrine / pharmacology
Ephedrine / therapeutic use*
Female
Flow Cytometry
Interleukin-10 / blood
Interleukin-10 / metabolism*
Interleukin-12 / antagonists & inhibitors
Interleukin-12 / blood
Interleukin-6 / antagonists & inhibitors
Interleukin-6 / blood
Lipopolysaccharides / pharmacology*
Macrophages, Peritoneal / drug effects*
Macrophages, Peritoneal / immunology
Mice
Mice, Inbred C57BL
Nitric Oxide / biosynthesis
Sepsis / blood
Sepsis / immunology
Sepsis / prevention & control*
Tumor Necrosis Factor-alpha / antagonists & inhibitors
Tumor Necrosis Factor-alpha / blood

Substances

Anti-Inflammatory Agents, Non-Steroidal
Chemokine CXCL2
Cxcl2 protein, mouse
IL10 protein, mouse
Interleukin-6
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Interleukin-10
Interleukin-12
Nitric Oxide
Ephedrine