Pharmacologic Evaluation of Sulfasalazine, FTY720, and Anti-IL-12/23p40 in a TNBS-Induced Crohn’s Disease Model

Abstract

2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis has been used as an inflammatory bowel disease (IBD), Crohn's disease (CD), preclinical model. However, published data on pharmacologic and therapeutic efficacy testing of this model are limited. FTY720 inhibits lymphoid cell trafficking in inflammatory conditions and is of interest to treat IBD. We investigated the pharmacologic therapeutic efficacy of sulfasalazine, FTY720, and anti-IL-12/23p40, in a TNBS CD model. Female, 7-week-old, BALB/c mice were given sulfasalazine orally (PO) and intraperitoneally (IP) at 10mg/kg, FTY720 at 3mg/kg PO, and mouse anti-IL-12/23p40 at 25mg/kg IP. Vehicle groups given PO either phosphate-buffered saline/water or 40% ethanol served as controls. Pharmacologic efficacy was assessed using body weight loss, clinical scores of diarrhea and intestinal gross pathology, and colon weight parameters. Sulfasalazine and FTY720 treatment did not prevent body weight loss or reduce clinical scores of diarrhea or intestinal gross pathology, when compared with vehicle treatment. However, anti-IL-12/23p40 treatment showed significant efficacy by preventing body weight loss, reducing clinical scores of diarrhea, and reducing intestinal gross pathologic lesions, when compared with vehicle-treated animals. Sulfasalazine, anti-IL-12/23p40, and FTY720 were not effective in reducing colon weight. With the exception of anti-IL-12/23p40, sulfasalazine, and FTY720 did not demonstrate full pharmacologic efficacy in our TNBS CD model.