Crosstalk between interleukin-6 and corticotropin-releasing factor modulate submucosal plexus activity and colonic secretion

Brain Behav Immun. 2013 May;30:115-24. doi: 10.1016/j.bbi.2013.01.078. Epub 2013 Jan 29.


Background: Irritable bowel syndrome (IBS) is a common disorder of the gut with symptoms such as diarrhoea, constipation, abdominal pain and bloating, that are frequently exacerbated by stress. Circulating levels of the pro-inflammatory cytokine, interleukin-6 (IL-6), which can activate colonic enteric neurons, are elevated in IBS patients. These studies aim to explore the relationship between IL-6 and the stress peptide, corticotropin-releasing factor (CRF) in colonic submucosal neurons.

Methods: Calcium imaging, Ussing chamber electrophysiology and immunohistochemistry were conducted on rat distal colons to investigate potential crosstalk between IL-6 and CRF.

Key results: Colonic secretions from the maternal separation rat model of IBS stimulated increases in intracellular calcium in naïve submucosal neurons via CRF1 receptors (n=15, p<0.05). Moreover, IL-6 (n=50, p<0.01) but not IL-1β (n=46, p>0.05) or TNFα (n=46, p>0.05) potentiated the CRF-evoked calcium response. CRF (1μM, 1h, n=5) stimulation also induced colonic secretion of IL-6 and inhibited the pro-secretory effects of IL-6 on colonic ion transfer (n=12).

Conclusions and inferences: These studies demonstrate the modulatory effects of CRF on colonic IL-6 secretion, neuronal activation and secretory function. These findings may provide an insight into the molecular mechanisms underlying symptom flares in IBS during periods of high stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Colon / drug effects
  • Colon / metabolism*
  • Colon / physiopathology
  • Corticotropin-Releasing Hormone / metabolism
  • Corticotropin-Releasing Hormone / pharmacology*
  • Female
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology*
  • Irritable Bowel Syndrome / metabolism*
  • Irritable Bowel Syndrome / physiopathology
  • Male
  • Maternal Deprivation
  • Neurons / drug effects
  • Neurons / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • Receptors, Interleukin-6 / metabolism
  • Signal Transduction / drug effects
  • Submucous Plexus / drug effects
  • Submucous Plexus / metabolism*
  • Submucous Plexus / physiopathology


  • Interleukin-6
  • Receptors, Corticotropin-Releasing Hormone
  • Receptors, Interleukin-6
  • Corticotropin-Releasing Hormone
  • Calcium