Pituitary-adrenal and interleukin-6 responses to recombinant interleukin-1 in neonatal rats

The cytokine interleukin-1 (IL-1) is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis. During postnatal development, the rat appears to be hyporesponsive to many stimuli which activate the HPA system in adulthood. Since hyporesponsiveness depends to a large extent on the stimulus, these experiments investigated the ontogeny of the HPA axis and interleukin-6 (IL-6) responses to IL-1 beta. Six-, 9-, and 18-day-old pups were injected with human recombinant IL-1 beta and plasma ACTH, corticosterone (CORT) and IL-6 levels were measured. IL-1 beta administration resulted in age-dependent endocrine and immune responses. The younger neonates secreted less ACTH and CORT and more IL-6. This was not due to a lowered capacity of the pituitary to synthesize and secrete ACTH since peptide levels following adrenalectomy did not reveal age differences. These data suggest that the diminished response to IL-1 beta is due to the immaturity of neural circuits which may be required to fully activate the HPA axis to immune signals.