title: The Severity of Cecal Ligature and Puncture-Induced Sepsis Correlates with the Degree of Encephalopathy, but the Sepsis Does Not Lead to Acute Activation of Spleen Lymphocytes in Mice.
abstract: Septic encephalopathy represents the most frequently observed form of encephalopathy in intensive care units. Interactions between the immune and nervous systems have been observed in experimental sepsis. Therefore, the aim of the current study was to characterize the effect of different severities of sepsis on encephalopathy and the inflammatory profile of the spleen. We hypothesized that different grades of sepsis severity would lead to variations in encephalopathy and activation of spleen cells. We induced sepsis of different severities in Balb/c mice by cecal ligature and puncture (CLP). Six and 12 h after CLP induction, behavioral impairment was assessed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) test. The animals were then killed, and the plasma, spleen, and hippocampus were removed. Levels of the encephalopathy marker S100β were measured in plasma. Spleens were weighed and then a characterization of splenic lymphocytes was performed by flow cytometry (cytotoxic T lymphocyte, T helper lymphocytes, B lymphocytes, T regulatory cells, and Th17 cells). Cytokine levels in the spleen and hippocampus were determined by enzyme-linked immunosorbent assay (ELISA), and cytokine levels in plasma were performed with MilliPlex® technology. Our results showed that behavioral impairment as measured by the SHIRPA test and elevation in plasma S100β levels were significant in moderate and severe CLP groups compared to those in the sham control group. Regarding immunological alterations, we were unable to observe changes in the weights of the spleen and the profile of lymphocytes 6 h after CLP. However, several cytokines, including IL-6, IL-10, and IL-1β, were increased in spleen and plasma. In conclusion, we observed variations in encephalopathy as measured by plasma S100β, which were mediated by the severity of sepsis; however, we did not observe a different activation of spleen cells 6 h post-CLP, despite evidence of inflammation. Taken together, our data indicate that the severity of sepsis impacts the brain in absence of a change in the spleen lymphocyte profile.
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: http://orcid.org/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: J L
authors.initials: JL
authors.lastname: Machado
authors.affiliation: Laboratório de Investigação Médica - LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: W A
authors.initials: WA
authors.lastname: Barroso
authors.affiliation: Laboratório de Investigação Médica - LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: S K
authors.initials: SK
authors.lastname: Ariga
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: D000818:Animals; D001522:Behavior, Animal; D001927:Brain Diseases / Q000097:blood / Q000473:pathology*; D002432:Cecum / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D008026:Ligation; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D009929:Organ Size; D011677:Punctures; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D018805:Sepsis / Q000097:blood / Q000209:etiology*; D012720:Severity of Illness Index; D013154:Spleen / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D064568:S100 Calcium Binding Protein beta Subunit
keywords: Inflammation; Lymphocytes; SHIRPA; Sepsis; Septic encephalopathy