Abstract 271
Neonatal Disease Oriented Research: Steroids & Oxygen: Perinatal Effects Poster Symposium, Sunday, 5/2
Synthetic glucocorticoids (GC) reduce chronic lung disease after severe neonatal respiratory distress syndrome in preterm infants. However, we have shown previously that neonatal GC treatment induces long-term changes in the maturation of T lymphocytes and in the phenotype of hypothalamic corticotropin-releasing hormone neurons1. In the present study the long-term effects of neonatal GC treatment were investigated on susceptibility and severity of an inflammatory autoimmune disease, experimental autoimmune encephalomyelitis (EAE). Moreover, the long-term effects of early neonatal GC treatment were examined on the LPS-induced corticosterone (CORT) response in adult rats. Rats pups were treated (i.p.) with dexamethasone-phosphate (DEX-group) on neonatal day one (0.5 µg/g), day two (0.3 µg/g), and day three (0.1 µg/g). These doses were proportional to doses used in our hospital for treatment of preterm infants. Control pups were included, which were treated with equivalent doses of saline (SAL-group), or which were left untreated (UNTR-group). The disease EAE was induced at 8 weeks of age by injection of myelin basic protein in CFA. The results show that rats treated neonatally with DEX had increased severity of EAE as compared to the controls (p≤0.01), with a higher number of animals with disease score ≥ 2 in the DEX-group than in the SAL-group (73% vs. 35% resp., p≤0.01). The LPS-induced CORT response was tested at the same age. At 120 minutes after injection of LPS (2.5 µg/kg, i.p.), animals in DEX-group had enhanced LPS-induced CORT plasma levels as compared to the control animals (p≤0.01). In conclusion, early neonatal DEX treatment persistently alters immune as well as endocrine functioning in adult life. Our data suggest that early neonatal GC therapy may be a risk factor for development of autoimmune disease in later life.
