title: Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve.
abstract: The immune system in vertebrates senses exogenous and endogenous danger signals by way of complex cellular and humoral processes, and responds with an inflammatory reaction to combat putative attacks. A strong protective immunity is imperative to prevent invasion of pathogens; however, equivalent responses to commensal flora and dietary components in the intestine have to be avoided. The autonomic nervous system plays an important role in sensing luminal contents in the gut by way of hard-wired connections and chemical messengers, such as cholecystokinin (CCK). Here, we report that ingestion of dietary fat stimulates CCK receptors, and leads to attenuation of the inflammatory response by way of the efferent vagus nerve and nicotinic receptors. Vagotomy and administration of antagonists for CCK and nicotinic receptors significantly blunted the inhibitory effect of high-fat enteral nutrition on hemorrhagic shock-induced tumor necrosis factor-alpha and interleukin-6 release (P < 0.05). Furthermore, the protective effect of high-fat enteral nutrition on inflammation-induced intestinal permeability was abrogated by vagotomy and administration of antagonists for CCK and nicotinic receptors. These data reveal a novel neuroimmunologic pathway, controlled by nutrition, that may help to explain the intestinal hyporesponsiveness to dietary antigens, and shed new light on the functionality of nutrition.
authors.affiliation: Department of Surgery, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), University of Maastricht, 6200 MD, Maastricht, Netherlands. m.luyer@ah.unimaas.nl
authors.forename: Misha D
authors.initials: MD
authors.lastname: Luyer
authors.forename: Jan Willem M
authors.initials: JW
authors.lastname: Greve
authors.forename: M'hamed
authors.initials: M
authors.lastname: Hadfoune
authors.forename: Jan A
authors.initials: JA
authors.lastname: Jacobs
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Dejong
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D016207:Cytokines / Q000097:blood; D004041:Dietary Fats / Q000378:metabolism* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014630:Vagus Nerve / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D015850:Interleukin-6; D011949:Receptors, Cholecystokinin; D011978:Receptors, Nicotinic; D014409:Tumor Necrosis Factor-alpha