Prevention of dexamethasone-induced lymphocytic apoptosis in the intestineand in Peyer patches by enteral nutrition

Background Apoptosis is a programmed cell death, genetically controlled, th at can be activated by physiological and pathophysiological events and by t he administration of several drugs, including the exogenous administration of corticosteroids. The aim of this study was to develop a rat model of int estinal lymphocytic apoptosis induced by dexamethasone to determine if apop tosis could be prevented by enteral or parenteral nutrition. Methods: Male Sprague-Dawley rats were used. On day 0, the right internal jugular vein wa s catheterized for parenteral nutrition, and a silicone tube was inserted i nto the duodenum for enteral feeding. Animals (n = 6/group) were randomly a ssigned to one of the following 3 feeding regimens: an immune-enhancing ent eral diet; its placebo (the same formula without immunonutrients); and isoc aloric isonitrogenous parenteral nutrition. On the seventh day, 200 mug of dexamethasone or vehicle were administered by IV bolus, and the diets were continued for I more day. Intestinal Peyer patches and thymic lymphocytic a poptosis were determined both by flow-cytometry and immumohistochemistry. R esults: A single dexamethasone dose (200 mug/rat) administered to surgicall y treated rats fasted for 18 hours, 24 hours later, caused massive intestin al and Peyer patches lymphocytic apoptosis (96 +/- 2% and 85 +/- 5%, respec tively; p < .0001 versus vehicle in both kinds of tissue). Lymphocytic apop tosis was reduced to almost indetectable levels in intestinal and lamina pr opia lymphocytes (from 96 2% to <0.6%; p < .0001). Peyer patches lymphocyti c apoptosis was reduced as well (from 85 +/- 5% to 15 +/- 7.1%; p < .001) i n animals prefed the 2 enteral nutrition formulas. Those prefed parenteral nutrition only showed a partial decrease of lymphocytic apoptosis in the in testine (from 96 2% to 53 +/- 23%; p < .001). Nutrition had no effect on th e dexamethasone-induced thymus involution. Conclusions: Enteral nutrition p revents intestinal intraepithelial and lamina propia lymphocytic apoptosis due to dexamethasone. These findings support the use of early enteral nutri tion in critically ill patients treated with corticosteroids.