Alterations in the pituitary-adrenal axis of adult mice following neonatal exposure to interleukin-1.
Interleukin-1 (IL-1), a cytokine mainly derived from activated cells of the macrophage lineage, can stimulate the hypothalamus-pituitary-adrenal (HPA) axis. Acute and long-lasting effects on the HPA axis were induced by the administration of low doses of IL-1 to mice during the first 5 days of life. In 5-day-old mice, corticosterone blood levels were markedly elevated 2 h following the last injection of IL-1. IL-1-treated mice grew normally. When studied during adulthood, however, these animals showed a reduction in morning values of corticosterone and the ACTH/corticosterone ratio was increased. Furthermore, an inverse correlation between ACTH and corticosterone levels in blood and between ACTH content in the pituitary gland and corticosterone levels was observed in IL-1-treated mice. Lower blood levels of corticosterone were not due to a reduced sensitivity of the adrenal glands, because these animals responded normally to exogenous ACTH. Another alteration observed in IL-1-exposed adult mice was a reduction in ACTH-like immunoreactivity in the pituitary gland following acute cold and restraint stress. It is concluded that exposure of mice to IL-1 early in life causes long-lasting alterations in the HPA axis. Spleen cells from adult mice treated with IL-1 at birth also developed a stronger response to allogeneic antigens than did cells from control mice. This observation indicates the relevance of immune-neuroendocrine interactions during development.
del Rey
A
A
Institute of Physiology, Medical Faculty, Philipps University, Marburg, Germany.
Furukawa
H
H
Monge-Arditi
G
G
Kabiersch
A
A
Voigt
K H
KH
Besedovsky
H O
HO
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D009490:Neurosecretory Systems / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000254:growth & development; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology
D007375:Interleukin-1; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone