Stress and animal models of inflammatory bowel disease-An update on the role of the hypothalamo-pituitary-adrenal axis

Chronic psychosocial stress has been repeatedly shown in humans to be a risk factor for the development of several affective and somatic disorders, including inflammatory bowel diseases (IBD). There is also a large body of evidence from rodent studies indicating a link between stress and gastrointestinal dysfunction, resembling IBD in humans. Despite this knowledge, the detailed underlying neuroendocrine mechanisms are not sufficiently understood. This is due, in part, to a lack of appropriate animal models, as most commonly used rodent stress paradigms do not adequately resemble the human situation and/or do not cause the development of spontaneous colitis. Therefore, our knowledge regarding the link between stress and IBD is largely based on rodent models with low face and predictive validity, investigating the effects of unnatural stressors on chemically induced colitis. These studies have consistently reported that hypothalamo pituitary adrenal (HPA) axis activation during stressor exposure has an ameliorating effect on the severity of a chemically induced colitis. However, to show the biological importance of this finding, it needs to be replicated in animal models employing more clinically relevant stressors, themselves triggering the development of spontaneous colitis. Important in view of this, recent studies employing chronic/repeated psychosocial stressors were able to demonstrate that such stressors indeed cause the development of spontaneous colitis and, thus, represent promising tools to uncover the mechanisms underlying stress-induced development of IBD. Interestingly, in these models the development of spontaneous colitis was paralleled by decreased anti-inflammatory glucocorticoid (GC) signaling, whereas adrenalectomy (ADX) prior to stressor exposure prevented its development. These findings suggest a more complex rote of the HPA axis in the development of spontaneous colitis. In the present review I summarize the available human and rodent data in order to provide a comprehensive understanding of the biphasic role of the HPA axis and/or the GC signaling during stressor exposure in terms of spontaneous colitis development. (C) 2011 Elsevier Ltd. All rights reserved.