Treatment with neurokinin-1 receptor antagonist reduces severity of inflammatory bowel disease induced by Cryptosporidium parvum

Inflammatory bowel disease (IBD) is a chronic, debilitating disorder of uncertain and perhaps multiple etiologies. It is believed to be due in part to disregulation of the immune system. Neuroimmune interactions may be involved in induction or maintenance of IBD. In the present study, we examined the potential role of a neurotransmitter, substance P, in a mouse model of IBD. We found that binding sites for substance P, and more specifically, neurokinin-1 receptors, were upregulated in intestinal tissue of mice with IBD-like syndrome. Dosing of mice with LY303870, a neurokinin-1 receptor antagonist, reduced the severity of IBD, and treatment of mice with preexisting IBD allowed partial healing of lesions. We hypothesize that blocking the binding of substance P to the neurokinin-1 receptor interrupts the inflammatory cascade that triggers and maintains intestinal lesions of IBD. Inflammatory bowel disease (IBD) affects up to 200 people per 100,000 in North America and Europe. This debilitating chronic illness results in a decreased quality of life for affected patients as well as increased health care costs (41). The pre-dominant histological characteristic of this disease is a recur-rent, chronic inflammation of segments of the gut, character