Interleukin-1 alpha and interleukin-1 beta stimulate adrenocorticotropin secretion in the rat through a similar hypothalamic receptor(s): effects of interleukin-1 receptor antagonist protein.
Numerous reports have demonstrated that interleukin-1 beta (IL-1 beta) is a potent secretagogue for adrenocorticotropin (ACTH) and that IL-1 alpha appears to be considerably less efficacious. To clarify apparent differences in the potency of IL-1 alpha vs. -beta on ACTH secretion from a functional perspective, the IL-1 receptor antagonist protein, IRAP, was utilized. Following administration to rats either intravenously (i.v.) or adjacent to the median eminence (intra-ME), IL-1 beta was approximately 8-fold more potent than IL-1 alpha. IRAP, delivered i.v. or intra-ME, inhibited ACTH secretion due to the administration of IL-1 alpha or -beta by the corresponding route. Similar amounts of IRAP were required to attenuate ACTH responses to approximately equieffective i.v. doses of IL-1 alpha (200 ng) or -beta (25 ng): IC50 for IRAP inhibition of IL-1 alpha vs. -beta was approximately 2.5 or 5.5 micrograms, respectively. At these IC50 doses, the ratios of IRAP/IL-1 were 12.5 and 220 for IL-1 alpha vs. -beta, respectively. These ratios are compatible with mediation by a type I-like IL-1 receptor. To compare these properties of the central IL-1 receptor to a peripheral type I IL-1 receptor in the same species, the IL-1-enhanced rat thymocyte comitogenesis assay was utilized. Thymocyte proliferation in response to equieffective doses of IL-1 alpha or -beta was similarly inhibited by IRAP:approximate IC50 for inhibition of IL-1 alpha vs. -beta was 12.5 or 25 ng/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Endocrine Neuroscience Laboratories, Minneapolis Medical Research Foundation, MN 55404.
S G
SG
Matta
K M
KM
Linner
B M
BM
Sharp
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007267:Injections; D007275:Injections, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008473:Median Eminence / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D003208:Concanavalin A; D000324:Adrenocorticotropic Hormone