Adrenocorticotropin release induced by intracerebroventricular injection of recombinant human interleukin-1 in rats: possible involvement of prostaglandin.
ACTH release induced by iv and intracerebroventricular (icv) injection of recombinant human interleukin-1 beta (IL-1 beta) or alpha (IL-1 alpha) was studied in conscious, unrestrained rats. A dose as small as 3 ng of IL-1 beta injected icv induced a significant rise in plasma ACTH levels, whereas 100 ng/100 g body wt (approximately 300 ng/rat) was needed for a significant ACTH response when injected iv. Intracerebroventricular administration of 30 ng IL-1 alpha tended to increase plasma ACTH levels, but not significantly. Intravenous injection of 1000 ng/100 g IL-1 beta induced a maximal response with a pronounced elevation of plasma ACTH levels at 10 and 30 min after injection, but plasma ACTH levels fell at 60 min post injection. On the other hand, icv injection of 30 ng IL-1 beta raised plasma ACTH levels at 10 min, reaching peak values between 30 and 60 min post injection, and plasma ACTH levels remained elevated for 2-3 h after injection. Pretreatment with indomethacin completely prevented the ACTH response induced by either iv or icv injection of IL-1 beta. Administration of indomethacin did not alter the elevation of plasma ACTH levels induced by immobilization stress, however. On the other hand, vagotomy did not alter the ACTH response to iv administered IL-1 beta. Neither iv nor icv injection of IL-1 beta in a dose which induced a maximal ACTH response altered plasma PRL levels. These findings strongly suggest that the brain is the primary site of action of IL-1 beta, and that IL-1 beta transmits the message of the immune system to the brain and, possibly, CRF neurons. It is also suggested that prostaglandins may be involved in this central action of IL-1 beta.
Katsuura
G
G
United States-Japan Biomedical Research Laboratories, Tulane University Hebert Center, Belle Chasse, Louisiana 70037.
Gottschall
P E
PE
Dahl
R R
RR
Arimura
A
A
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000502:physiology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology*
D007375:Interleukin-1; D011453:Prostaglandins; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D007213:Indomethacin