Effect of Interleukin-1beta on Pituitary-Adrenal Responses and Body Weight in Neonatal Rats: Interaction with Maternal Deprivation.
The hypothalamic-pituitary-adrenal (HPA) axis of the infant rat is normally hyporesponsive during postnatal days (pnd) four to fourteen. This interval is termed the stress hyporesponsive period (SHRP). The HPA axis, however, does respond to selective stimuli, such as interleukin-1beta (IL-1beta) during this period. Furthermore, maternal deprivation has been shown to alter the system so that it is responsive to mild stimuli. The present studies examined the interaction between 24 h of maternal deprivation and intraperitoneal administration of recombinant human (rh) IL-1beta (4 µg/kg) at 3 ages (i.e., pnd 6, 12, 18) during or after the SHRP. The results demonstrate that maternal deprivation modifies the response of the HPA axis induced by IL-1beta in an age-dependent fashion: 1) a greater response at pnd 6; 2) a quicker response at pnd 12; and 3) a suppressed response pattern at pnd 18. Moreover, these responses across ages differ as a function of maternal contact postinjection: 1) deprivation augments the ACTH and CORT response and maternal contact postinjection further augments this response at pnd 6; 2) deprivation increases the ACTH and CORT response to vehicle and the CORT response to IL-1beta in 12 day-old pups and the mother has a modest inhibitory effect; and 3) at pnd 18 deprivation leads to lower ACTH concentrations, but higher overall CORT levels and maternal contact postinjection effectively suppresses both the ACTH and CORT response to IL-1. These differences in the HPA response do not appear to be due to differences in the immune response. Plasma concentrations of endogenous rat IL-1beta determined 1 and 2 h after injection of rhIL-1beta were not modified by deprivation and were reduced at pnd 18 compared to pnd 6 and 12 in NDEP pups. Finally, IL-1beta reduced food intake, as reflected by a decrease in body weight, in deprived pups at all 3 ages. The findings in the present experiments suggest that there are additional pathways through which IL-1beta can act on the CNS to activate the HPA axis besides direct action at the hypothalamus.
Kent
S
Stanford University School of Medicine, Department of Psychiatry & Behavioral Sciences, Primate Facility 7-930T, Stanford, CA 94305-5095, U.S.A.
Tom
C
Levine
S