Abstract 1100 Neonatal Disease Oriented Research: Intestinal Development Platform, Saturday, 5/1

Since LCP's are known to modulate the inflammatory cascade in several experimental models, we hypothesized that supplementation of premature formula with LCP's would reduce the incidence of neonatal NEC. To investigate the effect of fatty acids on NEC and the inflammatory cascade, newborn rats were stressed with formula feeding (0.1 ml/3 hr, advanced 0.1 ml/feed every 24 hours) and asphyxia (50 sec nitrogen and 10 min cold exposure, twice daily) and followed for 48-96 hr. Rats were randomized to the following dietary groups: A) LCP's + nucleotides, B) control, and C) LCP's, and at the end of the protocol or onset of illness, intestine was processed for histological assessment of NEC. Additional outcome measures included plasma endotoxin (limulus amoebocyte lysate assay), and at 24 and 48 hours (prior to onset of disease), intestinal mRNA expression of iNOS, PLA2, and PAF receptor (RT-PCR normalized to B-actin), and degree of apoptosis (immunofluorescent-labelled TUNEL stain) in intestinal epithelium. We found that LCP supplementation reduced the incidence of NEC (8/24, p=0.031) compared to control (17/24) and A (13/23). In addition, LCP's reduced plasma endotoxinemia (25 ± 4 EU/ml, p less than 0.05) vs A (170 ± 28) and B (276 ± 39), and intestinal PLA2 mRNA expression at 24 hours (0.41 ± 0.09 molecules/gm tissue) vs A (0.82 ± 0.13) and B (0.68 ± 0.11). There was no statistical difference in PAF receptor expression at 24 or 48 hours (1.5 ± 0.3, molecules/gm tissue) vs A (1.9 ± 0.4) and B (2.1 ± 0.2). In addition, LCP's had no effect on intestinal iNOS mRNA expression or degree of apoptosis at any time point. We conclude that LCP supplementation reduces the incidence of NEC and endotoxin translocation in a neonatal rat model. We speculate that LCP's protect against intestinal mucosal injury in the neonatal model. Further study of the inflammatory response locally in the intestinal environment seems warranted. Supported by Wyeth-Ayerst Nutritionals.