title: Cholecystokinin-stimulated monocytes produce inflammatory cytokines and eicosanoids.
abstract: OBJECTIVE
  Plasma cholecystokinin increases with enteral feeding. Cholecystokinin increases intracellular calcium in lymphocytes/monocytes and is a lymphocyte co-mitogen. We hypothesize that decreased cholecystokinin production with "bowel rest" and parenteral nutrition may be beneficial in inflammatory bowel disease by down-regulating gut immune/inflammatory mechanisms. The majority of cells observed in mucosa of inflammatory bowel disease are monocytes and neutrophils. Cholecystokinin effect was therefore measured on monocyte production of proinflammatory mediators (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6) and neutrophil chemotaxins/activators (interleukin-8, granulocyte-macrophage colony stimulating factor, and leukotriene B4).
  
  
  METHODS
  Peripheral blood monocytes (0.5 x 10(6)) from healthy donors in 1 mL of RPMI 1640 plus 5% fetal calf serum were cultured for 24 h in 5% CO2 at 37 degrees C with 5 micrograms/mL endotoxin, 1 x 10(-7) M cholecystokinin, or no agonist. Supernatants were analyzed by ELISA for cytokines and leukotriene B4.
  
  
  RESULTS
  Endotoxin-stimulated monocytes produced 1130 pg/mL tumor necrosis factor versus 81 pg/mL for cholecystokinin, 612 pg/mL interleukin-1 versus 10 pg/mL, 694 pg/mL interleukin-6 versus 30 pg/mL, 4531 pg/mL of interleukin-8 versus 3848 pg/mL, 21 pg/mL granulocyte-macrophage colony stimulating factor versus 9 pg/mL, and 21 pg/mL leukotriene B4 versus 12 pg/mL. Controls produced no cytokines/eicosanoids (N = 8, p < 0.001).
  
  
  CONCLUSIONS
  Cholecystokinin increase with enteral feeding may up-regulate gut immune response. Cholecystokinin suppression with parenteral alimentation may decrease inflammatory mediator production.
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Cunningham
authors.forename: T A
authors.initials: TA
authors.lastname: Shaw-Stiffel
authors.forename: L H
authors.initials: LH
authors.lastname: Bernstein
authors.forename: T J
authors.initials: TJ
authors.lastname: Tinghitella
authors.forename: R E
authors.initials: RE
authors.lastname: Claus
authors.forename: D A
authors.initials: DA
authors.lastname: Brogan
authors.forename: M A
authors.initials: MA
authors.lastname: McMillen
mesh_terms: D002478:Cells, Cultured; D002766:Cholecystokinin / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000096:biosynthesis*; D004750:Enteral Nutrition; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology / Q000628:therapy; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016207:Cytokines; D015777:Eicosanoids; D002766:Cholecystokinin; D012844:Sincalide