Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by episodic bouts of altered bowel habit, bloating and abdominal pain, but the underlying pathophysiology is still poorly understood. There is an increase in circulating levels of both the proinflammatory cytokines IL-6 and 8 in IBS patients and as a consequence, altered cytokine profiles have been proposed as a biomarker of IBS. Furthermore, IL-6 and IL-8 can stimulate myenteric neurons. A relationship has been demonstrated between activation of central corticotropin-releasing factor (CRF)1 receptors and the stress-related exacerbation of IBS symptoms. Crosstalk between IL-6, IL-8 and CRF has also been postulated. These studies aim to determine if immune and/or stress factors induce colonic contractile activity.The distal colon was excised from Sprague Dawley (SD) rats and whole mount preparations of circular muscle were prepared. The colonic tissue was then suspended from a tension transducer in a tissue bath of CO 2 bubbled Krebs saline under 1g of tension and allowed to equilibrate. Mechanical signals from the muscle were amplified, recorded and analysed using Chart7.IL-6 induced a small but robust increase in contractile activity (0.02±0.009 mV, n=5) which was partially inhibited by the presence of the Na+ channel blocker, TTX (100nM, 0.01±0.001 mV, n=5, p<0.01).CRF (10nM) similarly induced a contraction of the colonic tissue (0.03±0.003 mV, n=4) and the response was similarly reduced in the presence of TTX (0.02±0.002 mV, n=4, p<0.01). IL-6 plus CRF together stimulated a larger contraction (0.04±0.003 mV, n=4) than IL-6 alone (0.02±0.002 mV, n=4, p<0.05). In these studies CRF (0.03±x0.003mV, n=4) evoked a contraction that was larger than the IL-6 effect (p<0.05) but was not different to the combined effect of the two reagents (p>0.05). Application of IL-8 evoked a robust increase in contractility, resulting in large, repetitive contractions (n=5,) with a frequency of 0.48±0.11 Hz (n=5). The frequency of contractions was increased by IL-8 (0.84±0.1 Hz n=5 P<0.01) and was attenuated in the presence of TTX (p<0.001) but not completely inhibited .The contractile responses evoked by IL-8 were significantly greater than those evoked by IL-6 ( p<0.001) but no further enhancement of the IL-8-evoked response was noted when IL-8 and IL-6 were co-applied. However, colonic contractility in the presence of all three reagents resulted in contractile response that was larger in amplitude than IL-6 (p<0.001), IL-8 (p<0.001) or CRF (p<0.001) alone.These data illustrate that IL-8, IL-6 and CRF have functional effects on colonic contractile activity and this is likely mediated by the myenteric. These findings provide evidence that immune and stress mediators can cause changes in gastrointestinal motility which may contribute to IBS-like symptoms.