title: Deletion of the ventral noradrenergic bundle obliterates the early ACTH response after systemic LPS, independently from the plasma IL-1β surge.
abstract: We have recently shown that total lesion of the ventral noradrenergic bundle (VNAB-X), enhanced the short-lived (<120 min) triggering effect of intra-arterially (i.a.) given IL-1β on plasma ACTH levels. In the present study we used the same VNAB-X paradigm to explore the mechanisms of the long-lived (480 min) LPS stimulatory effect on plasma ACTH, corticosterone (CORT) and IL-1β levels. In control rats, 25 μg kg(-1) LPS induced a 20-fold increase in ACTH and a 7-fold increase in CORT concentrations at 30 min, which continued to rise until 60 min, before receding to baseline at 480 min. In contrast, the plasma IL-1β concentration started to increase above undetectable levels only at 120 min. In VNAB-X animals, the early (30 min) ACTH/CORT response to LPS was completely blunted, and the ACTH surge was reduced by 75% at 60 min. However, the sustained hormonal response (120 to 480 min) was unaltered. Both the temporal pattern and the amplitude of the plasma IL-1β response were normal. We conclude that (1) the VNAB is involved in the early (first 60 min) ACTH/CORT response to systemic LPS, (2) plasma IL-1β does not appear to be associated with this early corticotropic activation and (3) the later stages of the ACTH/CORT response to LPS (60 to 480 min) appear to be independent of the VNAB control and may therefore involve different control mechanisms, in which the IL-1β, by this stage massively released in the blood, may play a major role.
authors.affiliation: Endocrinological Neurobiology Laboratory, URA 1197 CNRS, University of Montpellier-2, 34095, Montpellier Cedex 5, France.
authors.forename: L
authors.initials: L
authors.lastname: Givalois
authors.forename: S
authors.initials: S
authors.lastname: Gaillet
authors.forename: M
authors.initials: M
authors.lastname: Mekaouche
authors.forename: C
authors.initials: C
authors.lastname: Ixart
authors.forename: A F
authors.initials: AF
authors.lastname: Bristow
authors.forename: P
authors.initials: P
authors.lastname: Siaud
authors.forename: A
authors.initials: A
authors.lastname: Szafarczyk
authors.forename: F
authors.initials: F
authors.lastname: Malaval
authors.forename: I
authors.initials: I
authors.lastname: Assenmacher
authors.forename: G
authors.initials: G
authors.lastname: Barbanel