00270-A: In Vitro Immunosuppressive Effects of Metronidazole on Canine Lymphocytes

Grant Amount: $12,096

Albert E. Jergens, DVM, PhD; Iowa State University

February 1, 2005 - January 30, 2006

Sponsor(s):

Breed(s): -All Dogs

Research Program Area: Gastrointestinal Disease

Abstract

Immunosuppressive drugs are commonly administered to human and veterinary patients to control immune-mediated inflammatory diseases. Administration of a combination of immunomodulatory drugs with different mechanisms of action should result in more effective immunosuppression and fewer drug-induced adverse effects. Anecdotal evidence supports the use of corticosteroids, sulfasalazine, and metranidazole in the therapy of human and canine inflammatory bowel disease (IBD). Corticosteroids and sulfasalazine exert nonspecific immunomodulatory actions in IBD patients to inhibit cellular infiltration and the formation and function of various pro-inflammatory mediators. Metronidazole has been hypothesized to inhibit cellular immunity (and hence mucosal inflammation seen with IBD) although conclusive studies attesting to its immunomodulatory effects have not been performed. We propose to investigate the immunomodulating effects of metronidazole on mitogen-stimulaed proliferation of lymphocytes in blood collected from healthy dogs. Qualitative and quantitative evaluation of canine lymphocytes sub-population proliferation will be performed using two- color flow cytometric analysis. Because clonal expansion of lymphocytes is essential for antigen-induced immune responses, the ability of metronidazole to inhibit mitogen-stimulated lymphocyte proliferation provides an in vitro assessment of the effect of this drug on immune function. The results from this study will provide a rational basis for using metronidazole in immunosuppressive drug regimens for treatment of canine IBD.

Publication(s)

None at this time.