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Updated: May 14, 2026

Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
Published on: December 16, 2021
Crosstalk between interleukin-6 and corticotropin-releasing factor modulate submucosal plexus activity and colonic
Dervla O'Malley1, John F Cryan, Timothy G Dinan
1Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Physiology, University College Cork, Cork, Ireland. d.omalley@ucc.ie
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.
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