W1785 Enteropathogenic E. coli Non-Lee Encoded Effectors Nleh1/2 Fail to Suppress Inflammatory Response, in Contrast to Shigella Homolog Ospg

Abstract

injected with endotoxin (E. coli lipopolysaccharide (LPS)) or saline though the uterine wall. Pigs were given LPS via the amniotic fluid (LPS-a, 0.4 mg/kg, n=11), intramuscularly (LPSim, 0.014 mg/kg, n=16) or given saline intramuscularly (Saline-im, 0.5 ml, n=18). Five days after injection, piglets were delivered preterm by caesarean section and fed colostrum or infant formula. All pigs were sacrificed when clinical signs of NEC were evident in several litter-mate pigs (24-40 h postpartum). Blood gas and chemistry values were recorded and the gut was evaluated and scored for NEC lesions, villous/crypt morphology and brush border enzymes. None of the pigs fed colostrum developed NEC and showed the most favourable values for blood parametres and gut maturation (villous height, enzymes). Formula-fed LPS-a, LPS-im and saline-im showed NEC incidences of 18%, 55% and 56%, respectively. LPS-a had lower clinical NEC scores than LPS-im (p<0.05) and saline-im (p= 0.09) pigs. LPS-a also tended to have higher mean crypt depth and activities of sucrase, lactase, aminopeptidase A and N in the small intestine (all p<0.15) and lower lung density (p<0.05). Formula fed LPS-im pigs had higher blood pCO2 and lactate values and lower glucose values than LPS-a and saline-im (P<0.05). In conclusion, systemic exposure to endotoxin has minimal effects at the present dose. Conversely, prenatal luminal exposure to endotoxin moderately reduces NEC development, mucosal hypotrophy and digestive malfunction and may help lung development in preterm neonates. Such effects could be mediated via modulation of the mucosal immune system, making both lung and gut epithelia better able to cope with postnatal challenges. In this regard, luminal endotoxin exposure may work similar to the marked beneficial effects of colostrum on both NEC and epithelial immunity in preterm neonates.