Synergism between interleukins 1 beta and 6 on noradrenergic nerves in rat myenteric plexus

Gastroenterology. 1994 Oct;107(4):993-1001. doi: 10.1016/0016-5085(94)90223-2.


Background/aims: Because levels of interleukins 1 beta and 6 (IL-1 beta and IL-6) are elevated during intestinal Trichinella spiralis infection, they may mediate the changes in enteric neural function in that model. IL-1 beta suppresses norepinephrine release from the myenteric plexus, but the effect of IL-6 is unknown. Therefore, we investigated the effects of IL-6 alone and in combination with IL-1 beta on norepinephrine release.

Methods: Longitudinal muscle myenteric plexus or myenteric nerve varicosity preparations from jejunum of noninfected rats were loaded with [3H]norepinephrine, and 3H release was measured after a preincubation with or without human recombinant IL-6, alone or in combination with human recombinant IL-1 beta.

Results: 1 ng/mL of IL-6 augmented 3H release, 100 ng/mL suppressed 3H release, whereas 10 ng/mL had no effect. However, IL-6 (10 ng/mL) plus a subthreshold concentration of human recombinant IL-1 beta significantly suppressed 3H release, and this was abolished by adding anti-IL-6 antibody or an IL-1 receptor antagonist.

Conclusions: Because 3H release reflects [3H]norepinephrine release, our results show that IL-6 exerts a dual effect on norepinephrine release. Furthermore, there is synergism between IL-1 beta and IL-6 resulting in suppression of norepinephrine release. Therefore, both cytokines may contribute to the suppression of norepinephrine release observed in the inflamed intestine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Synergism
  • Female
  • Humans
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / pharmacology*
  • Male
  • Myenteric Plexus / drug effects*
  • Myenteric Plexus / metabolism*
  • Nervous System / metabolism
  • Norepinephrine / metabolism*
  • Osmolar Concentration
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins


  • Interleukin-1
  • Interleukin-6
  • Recombinant Proteins
  • Norepinephrine