CHOLECYSTOKININ-STIMULATED MONOCYTES PRODUCE INFLAMMATORY CYTOKINES AND EICOSANOIDS

Objectives: Plasma cholecystokinin increases with enteral feeding, Cho lecystokinin increases intracellular calcium in lymphocytes/monocytes and is a lymphocyte co-mitogen, We hypothesize that decreased cholecys tokinin production with ''bowel rest'' and parenteral nutrition may be beneficial in inflammatory bowel disease by down-regulating gut immun e/inflammatory mechanisms, The majority of cells observed in mucosa of inflammatory bowel disease are monocytes and neutrophils. Cholecystok inin effect was therefore measured on monocyte production of proinflam matory mediators (tumor necrosis factor alpha, interleukin-1 beta, int erleukin-6) and neutrophil chemotaxins/activators (interleukin-8, gran ulocyte-macrophage colony stimulating factor, and leukotriene B-4). Me thods: 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 mu g/mL endotoxin, 1 x 10(-7) M cholecys tokinin, or no agonist, Supernatants were analyzed by ELISA for cytoki nes and leukotriene B-4. Results: Endotoxin-stimulated monocytes produ ced 1130 pg/mL tumor necrosis factor versus 81 pg/mL for cholecystokin in, 612 pg/mL interleukin-1 versus 10 pg/mL, 694 pg/mL interleukin-6 v ersus 30 pg/mL, 4531 pg/mL of interleukin-8 versus 3848 pg/mL, 21 pg/m L granulocyte-macrophage colony stimulating factor versus 9 pg/mL, and 21 pg/mL leukotriene B-4 versus 12 pg/mL, Controls produced no cytoki nes/eicosanoids (N = 8, p < 0.001), Conclusion: Cholecystokinin increa se with enteral feeding may up-regulate gut immune response, Cholecyst okinin suppression with parenteral alimentation may decrease inflammat ory mediator production.