Elevation of plasma ACTH concentration in rabbits made febrile by systemic injection of bacterial endotoxin

This study was carried out to investigate the adrenocorticotropic hormone (ACTH) response in rabbits made febrile by systemic injection of lipopolysaccharide (LPS, Salmonella typhosa endotoxin). Intravenous (i.v.) injection of LPS (0.1 microgram/kg and 1.0 microgram/kg) increased rectal temperature (biphasic fever) and the plasma concentration of ACTH (ACTH response) in a dose-related manner. These responses were suppressed by pretreatment with indomethacin (20 mg/kg, subcutaneously). Intracerebroventricular (i.c.v.) administration of indomethacin (400 micrograms) had no effect on the ACTH response to LPS, although it significantly suppressed febrile response. Small increases in plasma concentration of ACTH and significant fevers followed i.c.v. administration of prostaglandin E2 (2 micrograms) or F2 alpha (2 micrograms). I.v. administration of corticotropin releasing factor (CRF) antagonist [alpha-helical CRF (9-41) (200 micrograms/kg)] partly suppressed the ACTH increase induced in plasma by i.v. LPS. These results suggest that prostaglandins synthesized outside the blood-brain barrier play an important role in the ACTH response and that the mechanism for induction of the ACTH response is not exactly the same as that for the febrile response, although prostaglandins are involved in both responses.