caa a22 4500 445796316 CHVBK 20180317145126.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s10620-011-1628-8 doi (NATIONALLICENCE)springer-10.1007/s10620-011-1628-8 Pharmacologic Evaluation of Sulfasalazine, FTY720, and Anti-IL-12/23p40 in a TNBS-Induced Crohn's Disease Model [Elektronische Daten] [Zaher Radi, Deborah Heuvelman, Jaime Masferrer, Ericka Benson] Background: 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. Aim: We investigated the pharmacologic therapeutic efficacy of sulfasalazine, FTY720, and anti-IL-12/23p40, in a TNBS CD model. Methods: 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. Results: 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. Conclusion: With the exception of anti-IL-12/23p40, sulfasalazine, and FTY720 did not demonstrate full pharmacologic efficacy in our TNBS CD model. Springer Science+Business Media, LLC, 2011 IBD nationallicence TNBS nationallicence Sulfasalazine nationallicence FTY720 nationallicence Anti-IL-12/23p40 nationallicence Radi Zaher Drug Safety R&D, Pfizer Worldwide Research and Development, 35 CambridgePark Dr, 02140, Cambridge, MA, USA aut Heuvelman Deborah Drug Safety R&D, Pfizer Worldwide Research and Development, 35 CambridgePark Dr, 02140, Cambridge, MA, USA aut Masferrer Jaime Drug Safety R&D, Pfizer Worldwide Research and Development, 35 CambridgePark Dr, 02140, Cambridge, MA, USA aut Benson Ericka Drug Safety R&D, Pfizer Worldwide Research and Development, 35 CambridgePark Dr, 02140, Cambridge, MA, USA aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/8(2011-08-01), 2283-2291 0163-2116 56:8<2283 2011 56 10620 https://doi.org/10.1007/s10620-011-1628-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-011-1628-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Radi Zaher Drug Safety R&D, Pfizer Worldwide Research and Development, 35 CambridgePark Dr, 02140, Cambridge, MA, USA aut NATIONALLICENCE 700 1- Heuvelman Deborah Drug Safety R&D, Pfizer Worldwide Research and Development, 35 CambridgePark Dr, 02140, Cambridge, MA, USA aut NATIONALLICENCE 700 1- Masferrer Jaime Drug Safety R&D, Pfizer Worldwide Research and Development, 35 CambridgePark Dr, 02140, Cambridge, MA, USA aut NATIONALLICENCE 700 1- Benson Ericka Drug Safety R&D, Pfizer Worldwide Research and Development, 35 CambridgePark Dr, 02140, Cambridge, MA, USA aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/8(2011-08-01), 2283-2291 0163-2116 56:8<2283 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer