The role of gut peptides such as CCK in the physiological regulation of energy homeostasis has been the main driver of recent enteroendocrine (EEC) research. However, apart from their contribution to maintaining mucosal integrity, little is known about the role of EEC in the response to intestinal inflammation. Gut inflammation is associated with reduced food intake and nutritional compromise. We have established that increased activity in the EEC system is a central component of this. In humans with upper gut infection plasma levels of the peptide CCK are significantly elevated, returning to normal following antimicrobial therapy. Modelling this in nematode models of murine enteritis has confirmed a role for CCK in the hypophagic response operating via the CCK1 receptor, presumably vagal. CCK cell hyperplasia is observed during the inflammatory response. This is directly effected by the immune response: immunoneutralisation of CD4+ T-lymphocytes abolishes both hypophagia and EEC hyperplasia, in an IL-4/13 dependent manner. This does not occur in immunodeficient SCID or nude mice, but the response can be adoptively transferred from immunocompetent animals and is independent of TNF-α. In addition, the EEC cell line STC-1 shows enhanced CCK secretion in response to nutrients when exposed to pro-inflammatory mediators. Preliminary data also indicate amplification in EEC function in human inflammatory bowel disease. These findings indicate that EEC may present therapeutic targets in the aetiology and management of reduced food intake observed in GI disease.