A study of gut immunity to enteral endotoxin in rats of different ages: a possible cause for necrotizing enterocolitis.

PURPOSE: Immature gut immunity can be a predisposing factor for necrotizing enterocolitis (NEC). The gut active immunity and innate defense to the Escherichia coli endotoxin lipopolysaccharide (LPS) in immature and mature rats were studied.

METHODS

LPS, started at a dose of 10 mg/kg, was instilled into the stomachs of fetal, newborn, 1-month and 3-month-old rats. Boost doses and normal saline control instillations were given on day 14. Rats that died after instillation had detailed postmortem examinations. For survivors, a group of 6 immunized and 6 controls were killed on day 7 for the collection of serum, spleens, mesenteric lymph nodes, and small intestines. Lymphocytes (10(6)) prepared from each tissue sample of individual group were cultured for 5 days. Serum and supernatant were analyzed for IgA and anti-E coli IgA levels.

RESULTS

All control rats survived. The doses of LPS given were 10, 5, 2.5, and 1.25 mg/kg. All fetal rats died after LPS instillation. Half-lethal dose for newborns was 2.5 mg/kg. One-month and 3-month-old rats survived all doses of LPS. The cause of death was endotoxemia. The serum IgA and total supernatant anti- E coli IgA levels of rats of all ages studied showed no significant difference.

CONCLUSION

The poor innate gut defense, not so much the active immunity, may provide an explanation for the susceptibility of the premature babies and newborn infants to the development of NEC.