Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1 alpha.
Recombinant human interleukin-1 alpha (rhIL-1 alpha) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1 alpha in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1 alpha administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1 alpha-induced increase in ACTH levels at the doses used. In fact, the rhIL-1 alpha-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus.
Perlstein
R S
RS
Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5603.
Mehta
N R
NR
Mougey
E H
EH
Whitnall
M H
MH
Neta
R
R
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014916:Whole-Body Irradiation
D007375:Interleukin-1; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone