In the rat, interleukin-1 alpha and -beta stimulate adrenocorticotropin and catecholamine release.
Recombinant interleukin-1 alpha and -beta (Il-1 alpha and -beta) have been evaluated for their abilities to stimulate ACTH and catecholamine secretion in the intact adult male rat. Additionally, the role of adrenergic-dependent pathways in mediating Il-1-induced ACTH release has been assessed. The iv or intracerebroventricular injection of either Il-1 alpha or Il-1 beta caused dose-related increases in plasma ACTH, epinephrine, and norepinephrine levels. While at low iv doses (less than or equal to 10 ng), Il-1 beta was more effective than Il-1 alpha at releasing ACTH, no measurable differences were noted at higher doses. In contrast, Il-1 beta was significantly more active at all doses in elevating plasma ACTH levels after intracerebroventricular injection. Similarly, Il-1 alpha was more effective than Il-1 beta at stimulating epinephrine, but not norepinephrine, secretion after icv injection. Because of the ability of catecholamines to alter ACTH secretion, we then examined the role of adrenergic-dependent pathways as possible mediators of Il-1-induced ACTH secretion. Blockade of adrenergic receptors by the concomitant administration of prazosin and propanolol prevented the simultaneous actions of phenylephrine and isoproterenol on the corticotrophs, but did not significantly alter the effect of peripherally administered Il-1 alpha on ACTH release. These results suggest that both Il-1 alpha and Il-1 beta stimulate ACTH and catecholamine secretion in the rat. Despite the ability of the lymphokine to elevate plasma epinephrine and norepinephrine values, circulating catecholamines do not appear to represent essential modulators of ACTH release induced by acutely injected Il-1.
Rivier
C
C
The Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Vale
W
W
Brown
M
M
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D007375:Interleukin-1; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D009638:Norepinephrine; D004837:Epinephrine