title: Evidence that a fast, rate-sensitive negative feedback effect of corticosterone is not a principal mechanism underlying the indomethacin inhibition of interleukin-1 beta-induced adrenocorticotropin secretion in the rat.
abstract: A number of previous studies have concluded that prostaglandins (PGs) play a crucial role in mediating the corticotropin-releasing hormone and adrenocorticotropin (ACTH) secretion induced by interleukin (IL) 1 beta in the rat. This is mainly based on a significant inhibitory effect of indomethacin, a cyclooxygenase inhibitor, on the hormonal response. However, there is one previous study which reported that such an inhibitory action of indomethacin on ACTH secretion is mediated principally by a fast, rate-sensitive negative feedback effect of corticosterone which increases after indomethacin injection, rather than by a decrease in PG production. In order to have a better understanding of this unresolved issue, in the present study the authors compared the effects of two different time intervals (10 or 20 min) between the intravenous injections of indomethacin (10 mg/kg body weight) and of recombinant human IL-1 beta (3 micrograms/kg body weight) on the cytokine-induced ACTH secretion in male rats. Although IL-1 beta-induced ACTH response was significantly suppressed by indomethacin given either 10 or 20 min before, the latter protocol led to a significantly greater inhibition of the hormonal response than the former. However, between the two groups, the rising slope of corticosterone from -20 or -10 min to time zero and that from time zero to 10 min after IL-1 beta injection were statistically indistinguishable. There results strongly suggest that the fast, rate-sensitive negative feedback effect of corticosterone may not be a principal mechanism whereby indomethacin inhibits IL-1 beta-induced ACTH secretion in the rat. It was concluded that such an action of indomethacin is primarily mediated by its inherent pharmacological action, i.e. the inhibition of endogenous PG production.
authors.affiliation: Third Department of Internal Medicine, Hirosaki University School of Medicine, Aomori, Japan. watanobe@infoaomori.ne.jp
authors.forename: H
authors.initials: H
authors.lastname: Watanobe
authors.forename: R
authors.initials: R
authors.lastname: Nasushita
authors.forename: S
authors.initials: S
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Suda
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
chemical_list: D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D007213:Indomethacin