Poster No. 169 AS101 Attenuates

the Severity of DSS- Induced Murine Colitis: Association with IL-17 Inhibition Gilad Halpert 1 , Yona Kalechman1, Lea Rath-Wolfson2, Benjamin check details Sredni1 1 Safdié Institute for AIDS and Immunology Research The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel, 2 Department of Pathology, Rabin Medical Center.Golda Campus, Petah Tikva, Israel Ulcerative colitis (UC) and Crohn’s disease (CD) are the major chronic inflammatory bowel diseases (IBD) affecting the gastrointestinal tract (GI). UC primarily affects the mucosal lining of the colon, whereas CD affects the whole GI. Defective mucosal barrier triggers invasion of commensal enteric bacteria into the gut layers that result in aggressive immune responses. Feeding mice for several days with Dextran Sodium Sulfate

(DSS) polymers in the drinking water induces acute colitis characterized by bloody diarrhea, ulceration, body weight loss and infiltration with granulocytes/mononuclear cells, reflecting human’s CHIR-99021 molecular weight symptoms. The present study was designed to explore the ability of the anti-inflammatory immunomodulator, ammonium tichloro [1,2-ethanediolato-O,O’] tellurate (AS101) to attenuate the severity of DSS-induced murine colitis. C57BL/6 mice received 3.5% w/v DSS in the drinking water for 7 days followed by 5 days of regular autoclaved water. Daily treatment with AS101 starting either concomitantly with DSS or 2 days later, significantly reduced occult and visible blood score vs. the

DSS+PBS group. Furthermore, both treatment modes with AS101 significantly ameliorated the stool consistency score and prevented the decrease in body weight. Colon length, being much reduced in Quisqualic acid diseased mice was normalized in AS101-treated mice. Histopathology examination of the distal colon revealed destruction of the crypt structure in PBS-treated mice. Furthermore massive mononuclear cell infiltration into the mucosa and submucosa were found. In comparison, the colons of AS101-treated mice exhibited normal appearance. Treatment with AS101, either before or after disease onset, significantly reduced the inflammatory cytokine IL-17 in the colon while only AS101 given concomitantly with DSS also reduced colonic INF-γ. These results collectively propose that inhibition of colon IL-17, and not that of INF-γ, plays an important role in attenuating murine colitis by AS101 and suggest that treatment with AS101 may be an effective therapeutic approach for controlling human IBD. Poster No.