An interleukin-1 beta-induced noradrenaline release in the spleen is mediated by brain corticotropin-releasing factor: an in vivo microdialysis study in conscious rats

Brain Behav Immun. 1994 Mar;8(1):14-23. doi: 10.1006/brbi.1994.1002.


The purpose of this study was to investigate whether an intraperitoneal injection of interleukin-1 beta (IL-1 beta) affects noradrenaline release in the spleen through its action on the brain of conscious rats. An in vivo microdialysis technique consisting of high-performance liquid chromatography with electrochemical detection was used for chronic monitoring of the splenic noradrenaline. The perfusion of a high concentration of K+ Ringer solution through the microdialysis probe significantly increased the concentration of noradrenaline in the spleen, while a perfusion of either Ca(2+)-free or tetrodotoxin-containing Ringer solution decreased the noradrenaline level in the dialysate. These results indicate that the noradrenaline recovered in the splenic dialysate is mainly derived from the nerve terminals of the splenic sympathetic nerve. The intraperitoneal injection of IL-1 beta (100 ng/kg) produced an immediate and significant increase in the noradrenaline levels in the spleen. The increased level reached a maximum level 40 min after injection and then gradually returned to the basal level. An intracerebroventricular (ICV) injection of a corticotropin-releasing factor (CRF) antagonist (alpha-helical CRF9-41, 30 micrograms) significantly attenuated the IL-1 beta-induced increase in the noradrenaline release. An ICV injection of CRF (2 micrograms) also caused a significant increase in splenic noradrenaline, which showed two distinct peaks at 20 and 140 min, respectively. These results suggest that the intraperitoneal injection of IL-1 beta facilitates noradrenaline release in the spleen through activation of the sympathetic nerve, and the increased sympathetic activity is, at least in part, due to the excitation of neurons containing CRF in the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Consciousness
  • Corticotropin-Releasing Hormone / administration & dosage
  • Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Corticotropin-Releasing Hormone / pharmacology
  • Corticotropin-Releasing Hormone / physiology*
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Interleukin-1 / administration & dosage
  • Interleukin-1 / pharmacology*
  • Male
  • Microdialysis
  • Neuroimmunomodulation / physiology*
  • Norepinephrine / metabolism*
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / pharmacology
  • Spleen / drug effects*
  • Spleen / innervation
  • Spleen / metabolism
  • Sympathetic Nervous System / physiology
  • Tetrodotoxin / pharmacology


  • Interleukin-1
  • Peptide Fragments
  • Recombinant Proteins
  • Tetrodotoxin
  • Corticotropin-Releasing Hormone
  • corticotropin releasing hormone (9-41)
  • Norepinephrine