Kanashiro Alexandre, Sônego Fabiane, Ferreira Raphael G, Castanheira Fernanda V S, Leite Caio A, Borges Vanessa F, Nascimento Daniele C, Cólon David F, Alves-Filho José Carlos, Ulloa Luis, Cunha Fernando Q
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil; Imagopole, Pasteur Institute, Paris, France.
Pharmacol Res. 2017 Mar;117:1-8. doi: 10.1016/j.phrs.2016.12.014. Epub 2016 Dec 12.
Sepsis is one of the main causes of mortality in hospitalized patients. Despite the recent technical advances and the development of novel generation of antibiotics, severe sepsis remains a major clinical and scientific challenge in modern medicine. Unsuccessful efforts have been dedicated to the search of therapeutic options to treat the deleterious inflammatory components of sepsis. Recent findings on neuronal networks controlling immunity raised expectations for novel therapeutic strategies to promote the regulation of sterile inflammation, such as autoimmune diseases. Interesting studies have dissected the anatomical constituents of the so-called "cholinergic anti-inflammatory pathway", suggesting that electrical vagus nerve stimulation and pharmacological activation of beta-2 adrenergic and alpha-7 nicotinic receptors could be alternative strategies for improving inflammatory conditions. However, the literature on infectious diseases, such as sepsis, is still controversial and, therefore, the real therapeutic potential of this neuroimmune pathway is not well defined. In this review, we will discuss the beneficial and detrimental effects of neural manipulation in sepsis, which depend on the multiple variables of the immune system and the nature of the infection. These observations suggest future critical studies to validate the clinical implications of vagal parasympathetic signaling in sepsis treatment.
脓毒症是住院患者死亡的主要原因之一。尽管近年来技术取得了进步，新一代抗生素也不断研发，但严重脓毒症仍是现代医学面临的重大临床和科学挑战。人们一直在努力寻找治疗脓毒症有害炎症成分的治疗方法，但均未成功。最近关于控制免疫的神经网络的研究结果，提高了人们对促进无菌性炎症（如自身免疫性疾病）调节的新型治疗策略的期望。有趣的研究剖析了所谓“胆碱能抗炎途径”的解剖学组成部分，表明电刺激迷走神经以及β-2肾上腺素能受体和α-7烟碱受体的药理激活可能是改善炎症状况的替代策略。然而，关于脓毒症等传染病的文献仍存在争议，因此，这种神经免疫途径的真正治疗潜力尚未明确界定。在这篇综述中，我们将讨论神经调节在脓毒症中的有益和有害影响，这取决于免疫系统的多个变量和感染的性质。这些观察结果提示未来需要进行关键研究，以验证迷走神经副交感神经信号在脓毒症治疗中的临床意义。
