Defective interleukin-1-induced ACTH release in cholestatic rats: Impaired hypothalamic PGE2 release

M. G. Swain, M. Maric, L. Carter

Research output: Contribution to journalJournal Articlepeer-review

26 Citations (Scopus)


A complete regulatory loop exists between the immune and neuroendocrine systems. Proinflammatory mediators such as endotoxin (lipopolysaccharide) and interleukin-1 (IL-1) are capable of activating the hypothalamic-pituitary- adrenal (HPA) axis at the hypothalamic level, presumably by inducing the synthesis of prostaglandins. We have recently identified abnormalities in the stress-induced activation of the HPA axis in cholestatic rats. Therefore, in rats with cholestasis due to bile duct resection and sham-resected controls, we studied alterations in proinflammatory mediator-induced activation of the HPA axis and documented the role of alterations in hypothalamic prostaglandin synthesis in these abnormalities. Systemic administration of endotoxin and IL-1 resulted in a significant attenuation of adrenocorticotropic hormone (ACTH) release into plasma in bile duct-resected compared with sham-resected animals. This suppression of endotoxin- or IL-1-induced ACTH release in bile duct-resected rats was associated with a complete absence of IL-1-induced hypothalamic release of prostaglandin E2 (PGE2) in vitro in these animals. In contrast, sham-resected rats exhibited a 70% increase in hypothalamic PGE2 secretion in vitro in response to IL-1. However, bile duct-resected rats exhibited HPA axis activation similar to that of sham-resected animals in response to intracerebroventricularly infused PGE2. Therefore, cholestasis in the rat is associated with an attenuation of central activation of the HPA axis by proinflammatory mediators that appears to be mediated, at least in part, by defective IL-1-induced hypothalamic prostaglandin production.

Original languageEnglish
Pages (from-to)G404-G409
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number3 31-3
Publication statusPublished - 1995


  • cytokine
  • neuroendocrine-immune axis
  • prostaglandin


Dive into the research topics of 'Defective interleukin-1-induced ACTH release in cholestatic rats: Impaired hypothalamic PGE2 release'. Together they form a unique fingerprint.

Cite this