Long-term Effects of Early Postnatally Administered Interleukin-1-beta on the Hypothalamic-Pituitary-Adrenal (HPA) Axis in Rats.
OBJECTIVE: Since perinatal stress events are well known to exert long-term influences on the function of hypothalamic-pituitary-adrenal (HPA) axis in rats, to investigate the consequences of exposure to IL-1, a potent stimulator of this axis, during early postnatal life. METHODS: Wistar rats were treated twice a day with 0.02 ug human recombinant IL-1 from day 1-4 of age, while controls received the vehicle only. RESULTS: IL-1 -treatment had no significant influence on the mortality and body weight. However, at the end of treatment period on the 4th day of life, the thymus weight was decreased in the IL-1 -treated group (P<0.01), while the adrenals were clearly enlarged (P<0.0002). These responses were associated with a nearly 4-fold elevation of the plasma corticosterone (CS) level as compared to vehicle-treated controls (P<0.001). At the age of seven months the stimulated CS levels induced by an acute stress (novel environment) were lower in rats treated neonatally with IL-1 than in controls (P<0.01). This functional disturbance was associated with morphological alterations in the parvicellular part of the paraventricular nucleus (PVN) which is the main hypothalamic regulation centre of the HPA axis. A strong reduction of the numerical density of neurons was found in the neonatally IL-1 -treated rats (P<0.005) while the neuronal nuclei were clearly enlarged (P<0.0005). CONCLUSION: As a part of an infection-induced stress response during critical periods of development, IL-1 might be capable of inducing a permanent structural malorganization of the PVN and, consequently, functional malprogramming of the HPA axis in rats.