Possible involvement of prostaglandin E in development of ACTH response in rats induced by human recombinant interleukin-1.
1. Intravenous (I.V.) injection of human recombinant interleukin-1 alpha (IL-1 alpha) produced dose-dependent monophasic fevers in rats. Moreover, the I.V. injection of IL-1 alpha produced dose-dependent rises in the plasma concentrations of adrenocorticotrophic hormone (ACTH) 30 min after injections with dosages of 5 micrograms/kg and 15 micrograms/kg of IL-1 alpha. 2. The febrile responses induced by the I.V. injection of IL-1 alpha (15 micrograms/kg) were completely abolished, and conversely hypothermia occurred, when the animals were pre-treated with a cyclo-oxygenase inhibitor, indomethacin (INDO). Pre-treatment with INDO also inhibited the increase in the plasma concentrations of ACTH induced by I.V. injection of IL-1 alpha (15 micrograms/kg), indicating that enhancement of plasma concentrations of ACTH induced by I.V. injection of IL-1 alpha is processed through the action of prostaglandins. 3. Intrapreoptic injection of prostaglandin E2 produced a dose-dependent fever with a rapid onset at doses of 25 and 100 ng. Moreover, the intrapreoptic injection of prostaglandin E2 increased the plasma concentrations of ACTH in a dose-dependent manner 30 min after injections. 4. The intrapreoptic injection of IL-1 alpha (20 ng) caused slow monophasic fever. However, no significant elevation of plasma concentrations of ACTH was observed 30, 90 and 180 min after the intrapreoptic injection of IL-1 alpha, as compared with the ACTH levels at each time in the control group which received an intrapreoptic injection of saline. 5. These results suggest that intrapreoptic prostaglandin E plays an important role in the ACTH response by inducing the release of corticotrophin-releasing factor (CRF).
Morimoto
A
A
Department of Physiology, Yamaguchi University School of Medicine, Japan.
Murakami
N
N
Nakamori
T
T
Sakata
Y
Y
Watanabe
T
T
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D005334:Fever / Q000209:etiology*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012007:Rectum
D007375:Interleukin-1; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D015232:Dinoprostone; D007213:Indomethacin