title: Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis.
abstract: 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.
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil. Electronic address: alex_bioquimica@yahoo.com.br.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kanashiro
authors.affiliation: 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.
authors.forename: Fabiane
authors.initials: F
authors.lastname: Sônego
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Raphael G
authors.initials: RG
authors.lastname: Ferreira
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Fernanda V S
authors.initials: FV
authors.lastname: Castanheira
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Caio A
authors.initials: CA
authors.lastname: Leite
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Borges
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Daniele C
authors.initials: DC
authors.lastname: Nascimento
authors.affiliation: Department of Immunology and Biochemistry, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: David F
authors.initials: DF
authors.lastname: Cólon
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Alves-Filho
authors.affiliation: Center of Immunology and Inflammation, Rutgers University - New Jersey Medical School, Newark, NJ 07103, USA. Electronic address: ulloalu@njms.rutgers.edu.
authors.forename: Luis
authors.initials: L
authors.lastname: Ulloa
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D018678:Cholinergic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy; D018805:Sepsis / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D018678:Cholinergic Agents
keywords: Adrenergic receptor; Inflammatory reflex; Nicotinic receptor; Sepsis; Vagus nerve