Plasma Interleukin-1β, Prolactin, ACTH and Corticosterone Responses to Endotoxin after Damage of the Anterior Hypothalamic Area

Abstract

This report concerns the use of an animal model described by us [J Submicrosc Cytol Pathol 1995;27:83–89] to investigate neural and endocrine sites for endotoxin (ENDO, E. coli 055:B5, 200 µg/100 g body weight in saline intravenously) effects on immunomodulatory hormone and cytokine release. Plasma interleukin-1β (IL-1β), prolactin (PRL), ACTH and corticosterone responses to ENDO after neurotoxic damage of neurons residing in the anterior hypothalamic area (AHA) were studied in freely behaving male rats. Excitotoxic cell damage in the AHA was produced by bilaterally injecting N-methyl-DL-aspartate (NMA) in artificial cerebrospinal fluid (aCSF) into this brain site. Injections of comparable volumes of aCSF alone served as controls for brain damage associated with the treatment. In both experimental brain manipulations before ENDO challenge the rise in plasma IL-1β concentrations in response to ENDO was reduced by 2-fold at 1 h and 3- to 5-fold at 3 h when compared to controls. Nevertheless, experimental and control brain manipulations did not modulate the expected rise in corticosterone concentrations after ENDO exposure which rose 5-fold above the baseline level in all animals. However, AHA manipulation did reduce plasma ACTH and prolactin concentrations differentially. Introduction of either NMA or the control injection of aCSF alone into AHA reduced plasma ACTH concentrations by 2-fold at 0.5 and 1 h after ENDO. However, there was a greater reduction in the rise of plasma PRL concentrations after ENDO found in NMA-treated groups versus rats receiving control aCSF. These results demonstrate that variable-size hypothalamic damage (a larger lesion produced in AHA by NMA treatment vs. a smaller lesion control after aCSF) can result in a differential blunting of PRL, IL-1β and ACTH release into blood in the face of robust, unmodulated corticosterone increases. In summary, these findings revealed a consistent predominant influence of ENDO on adrenal release of corticosterone as a concomitant to differential IL-1β, ACTH and PRL release after AHA cell loss. In conclusion, these results constitute further evidence for hypothalamic orchestration of a balance between immunotropic and immunosuppressive neuroendocrine-immune events during acute bacterial infection of mammals.

Lipopolysaccharide has selective actions on sub-populations of catecholaminergic neurons involved in activation of the hypothalamic–pituitary–adrenal axis and inhibition of prolactin secretion

“…The present results are in accordance with a recent study showing decreased plasma prolactin concentrations following immune activation (De Laurentiis et al 2002); however there are multiple other studies reporting either increased plasma prolactin concentrations (Rettori et al 1994, Phelps et al 2001, Gonzalez et al 2004 or no change in prolactin (Abreu et al 1994) following immune activation. The major difference between these conflicting results is the route of LPS administration or, in the case of Table 1.…”

“…In contrast, in studies using high doses of LPS given i.v. (Rettori et al 1994, Phelps et al 2001 or LPS given i.c.v. (Gonzalez et al 2004), LPS injection resulted in increased serum prolactin concentrations.…”