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

• Published in: Digestive diseases and sciences Vol. 56; no. 8; pp. 2283 - 2291
• Main Authors: Radi, Zaher A., Heuvelman, Deborah M., Masferrer, Jaime L., Benson, Ericka L.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.08.2011; Springer; Springer Nature B.V
• Subjects: Analysis; Animals; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Biochemistry; Biological and medical sciences; Body weight; Bones, joints and connective tissue. Antiinflammatory agents; Colitis; Crohn Disease - chemically induced; Crohn Disease - drug therapy; Crohn Disease - mortality; Diarrhea; Diarrhea - drug therapy; Disease Models, Animal; Feeding. Feeding behavior; Female; Fingolimod Hydrochloride; Fundamental and applied biological sciences. Psychology; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal Agents - pharmacology; Gastrointestinal Agents - therapeutic use; Health aspects; Hepatology; Interleukin-12 - antagonists & inhibitors; Interleukin-12 - immunology; Interleukin-23 - antagonists & inhibitors; Interleukin-23 - immunology; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Oncology; Organ Size - drug effects; Original Article; Other diseases. Semiology; Pharmacology. Drug treatments; Phosphates; Propylene Glycols - pharmacology; Propylene Glycols - therapeutic use; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; Sphingosine - therapeutic use; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Sulfasalazine; Sulfasalazine - pharmacology; Sulfasalazine - therapeutic use; Transplant Surgery; Trinitrobenzenesulfonic Acid - toxicity; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Weight Loss - drug effects; Sulfasalazine; IBD; TNBS; FTY720; Anti-IL-12/23p40; Fingolimod; Antiinflammatory agent; Interleukin 12; Metabolic diseases; Inflammatory disease; Immunomodulator; Crohn disease; Sulfonamides; Gastroenterology; Digestive diseases; Intestinal disease; Models; Salicylates; Immunosuppressive agent; Ulcerative colitis
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-011-1628-8

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 10 mg/kg, FTY720 at 3 mg/kg PO, and mouse anti-IL-12/23p40 at 25 mg/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.