Effects of repeated injections of interleukin 1β or lipopolysaccharide on the HPA axis in the newborn rat

The hypothalamic-pituitary-adrenal (HPA) axis is stimulated during immune and inflammatory processes. Interleukin 1 beta (IL-1 beta) and lipopolysaccharide (LPS) are known to be potent stimulators of this axis. During postnatal development, the rat seems to be hyporesponsive to many stimuli. The effects of repeated systemic injections of IL-1 beta and LPS on the HPA axis were investigated in neonatal rats. IL-1 beta (0.02 mu g/pup, administered twice daily from postnatal day 1 to 4) induced marked elevation in plasma corticosterone (CORT) level as compared to controls and LPS groups (0.4 mu g or 1.2 mu g LPS/pup, injected once daily from postnatal day 1 to 4), Adrenal wet weight was significantly higher, thymus weight was significantly lower. In contrast to the organ weights, there were no differences in CORT concentrations between LPS-exposed groups and controls, However, the weights of the adrenals in rats treated with LPS mere significantly increased in a dose-dependent manner as compared to controls. The high LPS dose was associated with significantly lower thymus weights as compared to controls and 0.4 mu g LPS rats. Thymus weights were significantly lower following IL-1 beta- than LPS-administration. It is supposed that a developing endotoxin tolerance could account for the observed absence of CORT rise after the last LPS injection. (C) 1999 Academic Press.