title: Corticotrophin-releasing factor as a mediator of the acute-phase response in rats, mice and rabbits.
abstract: The acute-phase response involves a number of separate physiological components, including induction of acute-phase protein synthesis by the liver. This response can be induced in vivo by administration of the endogenous leucocytic mediator interleukin-1 beta. A number of in-vivo effects of interleukin-1 beta have been reported to be mediated by corticotrophin-releasing factor (CRF), including activation of the hypothalamo-pituitary-adrenal axis and induction of fever, and in this report we have examined a possible involvement of CRF in mediating interleukin-1 beta-induced acute-phase protein synthesis. Interleukin-1 beta stimulated the elevation of species-specific plasma acute-phase proteins in rats, mice and rabbits. Co-injection of interleukin-1 beta with the specific CRF receptor antagonist alpha-helical-CRF9-41NH2 abolished or attenuated acute-phase protein synthesis induced by interleukin-1 beta in all three species for up to 12 h after injection. The inhibitory effect of alpha-helical-CRF9-41NH2 was reduced or absent 24 h after injection. Neutralizing anti-CRF antisera had no effect on acute-phase protein synthesis in the mouse and, paradoxically, potentiated acute-phase protein synthesis induced by interleukin-1 beta in the rat. These results indicate a possible mediatory role for CRF in regulation of acute-phase protein synthesis, and suggest that CRF may mediate induction of acute-phase protein synthesis by a different mechanism from that involved in regulation of corticotrophin secretion.
authors.affiliation: Division of Endocrinology, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, U.K.
authors.forename: P M
authors.initials: PM
authors.lastname: Hagan
authors.forename: S
authors.initials: S
authors.lastname: Poole
authors.forename: A F
authors.initials: AF
authors.lastname: Bristow
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D007106:Immune Sera; D007375:Interleukin-1; D010446:Peptide Fragments; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)