Treatment with Neurokinin-1 Receptor Antagonist Reduces Severity of Inflammatory Bowel Disease Induced by Cryptosporidium parvum

Author:

Sonea Ioana M.1,Palmer Mitchell V.2,Akili Dhuha1,Harp James A.2

Affiliation:

1. Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa 50011

2. National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa 50010

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Microbiology (medical),Clinical Biochemistry,Immunology,Immunology and Allergy

Reference47 articles.

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3. Bernstein, C. N., M. E. Robert, and V. E. Eysselein. 1993. Rectal substance P concentrations are increased in ulcerative colitis but not in Crohn's disease. Am. J. Gastroenterol.88:908-913.

4. Blum, A. M., A. Metwali, D. Elliot, M. Sandor, R. Lynch, and J. V. Weinstock. 1996. Substance P receptor antagonist inhibits murine IgM expression in developing schistosome granulomas by blocking the terminal differentiation of intragranuloma B cells. J. Neuroimmunol.66:1-10.

5. Blum, A. M., A. Metwali, M. Kim-Miller, J. Li, K. Qadir, D. E. Elliott, B. Lu, Z. Fabry, N. Gerard, J. V. Weinstock. 1999. The substance P receptor is necessary for a normal granulomatous response in murine Schistosomiasis mansoni. J. Immunol.162:6080-6085.

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