Neuroimmunomodulation in inflammatory bowel disease: How far from "bench" to "bedside"?

The chronic inflammatory bowel diseases (BID), Crohn's disease and ulcerative colitis, are characterized by recurrent periods of inflammation and tissue destruction. The clinical course is influenced by genetics, environmental factors, and the immune system. Recent insights (bench trials) benefiting from advances in genetic engineering and molecular biology have contributed to clinical care (bedside) in terms of actual or potential therapies. Does the neuroendocrine system significantly modify disease activity? Although conceptually appealing, evidence remains circumstantial. Compelling anecdotal reports exist that "stress" affects disease activity in terms of the frequency and severity of IBD flares (bedside), but the mechanisms underlying these observations are unknown. Evidence that neuroendocrine factors play a significant role in immunomodulation is progressing (bench), (i) Trinitrobenzene sulfonic acid (TNB)-induced colitis, although similar in unstressed Fisher and Lewis rats, shows marked worsening in stressed Lewis rats, (ii) Early studies of rectal pain perception suggest there are specific differences in neuroimaging studies (PET scans) in IBD patients compared to controls, (iii) Levels of substance P (SP) and its receptor are altered, (iv) Preliminary clinical studies with SP receptor antagonists show a trend toward improvement, (v) Importantly, the placebo response in clinical trials is as high as 45%. Evidence that neuroendocrine systems significantly modulate local inflammation is rapidly accumulating (bench), which will facilitate enhanced coordination of clinically relevant therapies (bedside).