Peer-Reviewed Journal Details
Mandatory Fields
O'Malley D, Cryan JF, Dinan TG
2013
January
Brain Behav Immun
Crosstalk between interleukin-6 and corticotropin-releasing factor modulate submucosal plexus activity and colonic secretion.
Published
()
Optional Fields
doi:pii: S0889-1591(13)00081-0. 10.1016/j.bbi.2013.01.078. [Epub ahead of print]

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 na´ve 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.

Grant Details