title: Splenic autonomic denervation increases inflammatory status but does not aggravate atherosclerotic lesion development.
abstract: The brain plays a prominent role in the regulation of inflammation. Immune cells are under control of the so-called cholinergic anti-inflammatory reflex, mainly acting via autonomic innervation of the spleen. Activation of this reflex inhibits the secretion of proinflammatory cytokines and may reduce the development of atherosclerosis. Therefore, the aim of this study was to evaluate the effects of selective parasympathetic (Px) and sympathetic (Sx) denervation of the spleen on inflammatory status and atherosclerotic lesion development. Female APOE*3-Leiden.CETP mice, a well-established model for human-like lipid metabolism and atherosclerosis, were fed a cholesterol-containing Western-type diet for 4 wk after which they were subdivided into three groups receiving either splenic Px, splenic Sx, or sham surgery. The mice were subsequently challenged with the same diet for an additional 15 wk. Selective Px increased leukocyte counts (i.e., dendritic cells, B cells, and T cells) in the spleen and increased gene expression of proinflammatory cytokines in the liver and peritoneal leukocytes compared with Sx and sham surgery. Both Px and Sx increased circulating proinflammatory cytokines IL-1β and IL-6. However, the increased proinflammatory status in denervated mice did not affect atherosclerotic lesion size or lesion composition.
  
  
  CONCLUSIONS
  Predominantly selective Px of the spleen enhances the inflammatory status, which, however, does not aggravate diet-induced atherosclerotic lesion development.
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; s.kooijman@lumc.nl.
authors.forename: Sander
authors.initials: S
authors.lastname: Kooijman
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands;
authors.forename: Illiana
authors.initials: I
authors.lastname: Meurs
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands;
authors.forename: Lianne
authors.initials: L
authors.lastname: van Beek
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands;
authors.forename: P Padmini S J
authors.initials: PP
authors.lastname: Khedoe
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands;
authors.forename: Annabel
authors.initials: A
authors.lastname: Giezekamp
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center; Leiden, The Netherlands;
authors.forename: Karin
authors.initials: K
authors.lastname: Pike-Overzet
authors.affiliation: Tytgat Institute for GI and Liver Disease, Academic Medical Center Amsterdam, The Netherlands; and.
authors.forename: Cathy
authors.initials: C
authors.lastname: Cailotto
authors.affiliation: Tytgat Institute for GI and Liver Disease, Academic Medical Center Amsterdam, The Netherlands; and.
authors.forename: Jan
authors.initials: J
authors.lastname: van der Vliet
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands;
authors.forename: Vanessa
authors.initials: V
authors.lastname: van Harmelen
authors.affiliation: Department of Gastroenterology, University Hospital Leuven, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Boeckxstaens
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands;
authors.forename: Jimmy F P
authors.initials: JF
authors.lastname: Berbée
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands;
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
mesh_terms: D000818:Animals; D053318:Apolipoprotein E3 / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D001341:Autonomic Nervous System / Q000502:physiology*; D003714:Denervation; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D012018:Reflex; D013154:Spleen / Q000276:immunology* / Q000294:innervation
chemical_list: D053318:Apolipoprotein E3; D053583:Interleukin-1beta; D015850:Interleukin-6
keywords: atherosclerosis; inflammation; splenic denervation; transgenic mice