title: The Role of Acetylcholine in the Inflammatory Response in Animals Surviving Sepsis Induced by Cecal Ligation and Puncture.
abstract: The cholinergic anti-inflammatory pathway controls the inflammatory response and nonreflexive consciousness through bidirectional communication between the brain and immune system. Moreover, brain acetylcholinesterase activity may have a role in regulating the vagus nerve in this pathway. Thus, we analyzed the role of acetylcholine (ACh) in the inflammatory response 15 days after induction of sepsis by cecal ligation and puncture (CLP). Balb/c mice were pretreated with or without donepezil (5 mg/kg/day, orally) 7 days before CLP, and mice homozygous for vesicular ACh transporter (VAChT) knockdown (KD) were subjected to CLP. All animals were sacrificed 15 days after CLP, and the plasma, spleen, and hippocampus were collected. Characterization of splenic lymphocytes and cytokine levels in the plasma, spleen, and hippocampus was determined. Our results showed a splenomegaly in group CLP. The numbers of cytotoxic T cells, helper T cells, regulatory T cells, B cells, and Th17 cells differed between mice subjected to CLP and to sham operation in both untreated and donepezil-treated groups. In VAChT-KD mice, CLP resulted in decreased cytotoxic and helper T cells and increased in Th17 cells compared with the sham. Additionally, in VAChT-KD mice, the levels of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, were increased following CLP. Thus, we concluded that ACh affected the inflammatory response at 15 days after CLP since stimulation of cholinergic transmission increased the proliferation of lymphocytes, including regulatory T cells, in association with a lower inflammatory profile and VAChT-KD decreased the number of lymphocytes and increased inflammation.
authors.affiliation: Laboratório de Investigação Médica - LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil. belacasagrandej@hotmail.com.
authors.forename: I C
authors.identifier: 0000-0002-7096-8004
authors.initials: IC
authors.lastname: Jeremias
authors.affiliation: Laboratório de Investigação Médica - LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: V J
authors.initials: VJ
authors.lastname: Victorino
authors.affiliation: Laboratório de Investigação Médica - LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: H V
authors.initials: HV
authors.lastname: Barbeiro
authors.affiliation: Laboratório de Investigação Médica - LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: S A
authors.initials: SA
authors.lastname: Kubo
authors.affiliation: Departmento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, Brazil.
authors.forename: C M
authors.initials: CM
authors.lastname: Prado
authors.affiliation: Laboratório de Investigação Médica - LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: T M
authors.initials: TM
authors.lastname: Lima
authors.affiliation: Laboratório de Investigação Médica - LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: F G
authors.initials: FG
authors.lastname: Soriano
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002432:Cecum / Q000473:pathology*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000473:pathology*; D008026:Ligation; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D009929:Organ Size; D011677:Punctures; D018805:Sepsis / Q000150:complications* / Q000473:pathology*; D013154:Spleen / Q000473:pathology; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D000109:Acetylcholine
keywords: Ach; Cytokines; Donepezil; Lymphocytes; Sepsis; VAChT