Activation of the hypothalamo-pituitary-adrenocortical axis in the conscious rabbit by the pyrogen polyinosinic:polycytidylic acid is dependent on corticotrophin-releasing factor-41.
The pyrogenic interferon inducer polyinosinic:polycytidylic acid (Poly I:C) was shown to activate the rabbit hypothalamo-pituitary-adrenocortical (HPA) axis in vivo. The immunoreactive cortisol response to Poly I:C (2.5 micrograms/kg) was shown to have a corticotrophin-releasing factor-41 (CRF-41)-dependent component which was abolished by peripheral immunoneutralization using an anti-CRF-41 monoclonal antibody (KCHMB001; 2.5 mg/kg i.v.). Peripheral administration of the arginine vasopressin (AVP) V1 receptor antagonist ([deamino-Pen1, O-Me-Tyr2, Arg8]-vasopressin; 225 nmol/kg i.v.) had no effect on the response of immunoreactive cortisol to Poly I:C, suggesting that AVP was not involved in activation of the HPA axis. Poly I:C increased both body temperature and circulating immunoreactive prostaglandin E2; these responses were abolished by the cyclo-oxygenase inhibitor ketoprofen (3 mg/kg s.c.). The immunoreactive cortisol response to Poly I:C, however, remained after the administration of ketoprofen, indicating a prostaglandin (PG)-independent component. The immunoreactive cortisol levels in control, saline vehicle-treated, animals were reduced by both the CRF-41 receptor antagonist (alpha-helical CRF (9-41); 6.25 nmol/kg i.v.) and ketoprofen (3 mg/kg s.c.) indicating that this basal state is dependent on both CRF-41 and PGs.
Milton
N G
NG
Department of Clinical Biochemistry, University of Newcastle upon Tyne, U.K.
Hillhouse
E W
EW
Milton
A S
AS
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007660:Ketoprofen / Q000494:pharmacology; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D011072:Poly U / Q000494:pharmacology*; D011749:Pyrogens / Q000494:pharmacology*; D011817:Rabbits; D013268:Stimulation, Chemical
D011749:Pyrogens; D011072:Poly U; D003346:Corticotropin-Releasing Hormone; D007660:Ketoprofen; C047490:poly(I).poly(c12,U); D015232:Dinoprostone; D011070:Poly I-C; D006854:Hydrocortisone