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Hyperactivity of the stress system and low‐grade immune activation characterize the functional bowel disorder irritable bowel syndrome (IBS).

These studies show that interleukin (IL)‐6 and IL‐8 and the stress hormone corticotropin‐releasing factor (CRF), present in IBS plasma, have functional effects on gastrointestinal activity by stimulating myenteric neurons and colonic contractions.

Moreover, in the Wistar Kyoto rat model of IBS, which exhibits altered gastrointestinal motility and visceral pain sensitivity, blocking IL‐6 and/or CRF1 receptors alleviates these IBS‐like symptoms.

Underlying these effects are altered colonic protein expression of tight junction proteins which regulate gut barrier function and the T‐type calcium channel Ca_V3.2, which has been linked to visceral pain.

These findings demonstrate the importance of the enteric nervous system and intestinal physiology in bowel dysfunction …