Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Int Immunopharmacol. 2012 May;13(1):46-53. doi: 10.1016/j.intimp.2012.03.005. Epub 2012 Mar 22.
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.
脓毒症及其衍生的内毒素性休克仍然是重症监护病房中死亡率较高的严重病症。确保促炎细胞因子和抗炎细胞因子产生平衡的机制尤其重要。盐酸麻黄碱（EH）作为一种有效的α-和β-肾上腺素能激动剂，是一种广泛用于心血管疾病的药物，特别是可以提升血压。在这里，我们证明 EH 通过激活 p38 MAPK 增加 Toll 样受体 4（TLR4）介导的白细胞介素 10（IL-10）的产生。同时，EH 负调控促炎细胞因子的产生。一致地，EH 增加脂多糖（LPS）诱导的血清 IL-10 并抑制体内肿瘤坏死因子-α（TNFα）的产生。因此，EH 治疗通过致命 LPS 挑战保护小鼠免受内毒素性休克。总之，我们的数据表明，EH 通过平衡 TLR4 信号中促炎细胞因子和抗炎细胞因子的产生，有助于免疫稳态。这项研究为 EH 在自身免疫性疾病或其他严重炎症中的潜在用途提供了依据。
