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: 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
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 13 Issue 1 Pg. 46-53 (May 2012) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 22446503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• 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

Topics

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