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.
Levine
S
S
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, California 94305.
Berkenbosch
F
F
Suchecki
D
D
Tilders
F J
FJ
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000097:blood; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone