Effect of the administration of cholecystokinin on the cholestasis associated with total parenteral nutrition in experimental short bowel

INTRODUCTION: Total parenteral nutrition (TPN) is not free of complications. One of the most serious is cholestasis; the cause of this complication is unclear but it may be due to a lack of an enteral stimulus for cholecystokinin (CCK) production. CCK is essential for contraction of the gallbladder and also stimulates intrahepatic bile flow. Its absence may contribute to cholestasis. After any hepatic aggression, the Kupffer cells respond and release proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF-alpha), which increase the hepatic damage. The objective of this experimental study has been to observe the effect that the exogenous administration of CCK could have on hepatic damage in experimental short bowel with and without TPN, determined using the serum levels of IL-1 and TNF-alpha. MATERIAL AND METHODS: A resection of 80% of the small bowel was performed on 53 Wistar rats and a continuous infusion of saline or TPN was initiated. The rats were divided into the following groups: SHAM (N = 14): normal saline infusion and free access to food and water. TPN (N = 15): Standard TPN. SHAM-CCK (N = 14): same as the SHAM group but with a daily dose of CCK. TPN-CCK (N = 10): same as the TPN group but with a daily dose of CCK. At the end of the experiment, the animals were sacrificed and blood samples were obtained to determine the IL-1 and TNF-alpha values by ELISA. RESULTS: The IL-1 and TNF-alpha levels were higher in the TPN group (7.537 and 5.899 pg/mL, respectively) than in the SHAM group (6.509 and 4.989 pg/mL, respectively) (p > 0.05). The TNF-alpha values were higher in the SHAM group (4.989 pg/mL) than in the SHAM-CCK group (4.583 pg/mL) (p < 0.001). The IL-1 and TNF-alpha levels were higher in the TPN group than in the TPN-CCK group (6.709 and 4.794 pg/mL, respectively) (p < 0.001 for TNF-alpha). CONCLUSIONS: 1. There is a rise in the serum levels of the pro-inflammatory cytokines IL-1 and TNF-alpha in animals with short bowel on TPN or enteral nutrition. 2. The administration of CCK causes a fall in the IL-1 and TNF-alpha levels, and could be used such as a further measure to prevent TPN-associated cholestasis.