title: CCK1-receptor stimulation protects against gut mediator-induced lung damage during endotoxemia.
abstract: OBJECTIVE
  Cholecystokinin 1-receptor (CCK1-R) activation by long chain fatty acid (LCFA) absorption stimulates vago-vagal reflex pathways in the brain stem. The present study determines whether this reflex also activates the cholinergic anti-inflammatory pathway, a pathway known to modulate cytokine release during endotoxemia.
  
  
  METHODS
  Mesenteric lymph was obtained from wild type (WT) and CCK1-R knockout (CCK1-R(-/-)) mice intraperitoneally challenged with Lipopolysaccharid (LPS) (endotoxemic lymph, EL) and intestinally infused with vehicle or LCFA-enriched solution. The lymph was analyzed for TNFα, IL-6 and IL-10 concentration and administered to healthy recipient mice via jugular infusion. Alveolar wall thickness, myeloperoxidase (MPO) and TUNEL positive cells were determined in lung tissue of recipient mice.
  
  
  RESULTS
  LCFA infusion in WT mice reduced TNFα concentration in EL by 49% compared to vehicle infusion, but had no effect in CCK1-R(-/-) mice. EL significantly increased the alveolar wall thickness, the number of MPO-positive and TUNEL-positive cells compared to control lymph administration. LCFA infusion in WT, but not in CCK1R(-/-) mice, significantly reduced these pathological effects of EL.
  
  
  CONCLUSIONS
  During endotoxemia enteral LCFA absorption reduces TNFα release into mesenteric lymph and attenuates histomorphologic parameters of lung dysfunction. Failure to elicit this effect in CCK1R(-/-) mice demonstrates that anti-inflammatory properties of LCFAs are mediated through CCK1-Rs.
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Eisner
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Martin
authors.forename: Markus A
authors.initials: MA
authors.lastname: Küper
authors.forename: Helen E
authors.initials: HE
authors.lastname: Raybould
authors.forename: Jörg
authors.initials: J
authors.lastname: Glatzle
mesh_terms: D000818:Animals; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005231:Fatty Acids, Unsaturated; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology*; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D043886:Receptor, Cholecystokinin A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D005231:Fatty Acids, Unsaturated; D015850:Interleukin-6; D008070:Lipopolysaccharides; D043886:Receptor, Cholecystokinin A; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009195:Peroxidase