Cholecystokinin and gastrin as immune modulating hormones: Implications and applications

Cholecystokinin (CCK) and gastrin are gastrointestinal hormones traditionally recognised for their roles in digestion. However, it has been recognised that these hormones may also modulate immune function. Here, we examine the immune-modulating effects of CCK and gastrin, and explore the functional significance of this dual role. In addition to the direct effect of these hormones on immune cell function, we discuss why hormones that regulate complex physiological and behavioural aspects of digestion might also influence immune responses. Notably, recent findings highlight the importance of these hormones in promoting a tolerogenic hepatic environment, particularly as the liver encounters gut-derived inflammogens following a meal. Additionally, the neuro-immune crosstalk mediated by CCK suggests that this hormone may influence immune responses indirectly via the gut-brain axis, especially in the context of infection or inflammation. Furthermore, the role of CCK in inducing feeding cessation and satiety appears to be repurposed during sickness behaviour, such as the loss of appetite during infection. Collectively, these observations suggest that nutritional strategies, including permissive underfeeding or fasting, could have important clinical implications. A deeper understanding of the dual roles of CCK and gastrin in digestion and immunity may pave the way for novel therapeutic approaches that leverage these pathways for improved disease management and treatment outcomes.