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Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2005; 11(43): 6843-6847
Published online Nov 21, 2005. doi: 10.3748/wjg.v11.i43.6843
Favorable response to subcutaneous administration of infliximab in rats with experimental colitis
John K Triantafillidis, Apostolos E Papalois, Aikaterini Parasi, Emmanuel Anagnostakis, Stavros Burnazos, Aristofanis Gikas, Emmanuel G Merikas, Emmanuel Douzinas, Maria Karagianni, Helen Sotiriou
John K Triantafillidis, Emmanuel Anagnostakis, Aristofanis Gikas, Emmanuel G Merikas, Department of Gastroenterology, “Saint Panteleimon” General State Hospital, Nicea, Greece
Apostolos E Papalois, Stavros Burnazos, Emmanuel Douzinas, Experimental Research Unit, ELPEN Company, Athens, Greece
John K Triantafillidis, Apostolos E Papalois, Aikaterini Parasi, Research Group of the Hellenic Society of Gastrointestinal Oncology, Greece
Aikaterini Parasi, Maria Karagianni, Helen Sotiriou, Department of Pathology, “Saint Panteleimon” General State Hospital, Nicea, Greece
Author contributions: All authors contributed equally to the work.
Correspondence to: John K Triantafillidis MD, 8, Kerasountos Street, 12461, Haidari, Athens, Greece. jkt@panafonet.gr
Telephone: +210-5819481 Fax: +210-5810790
Received: March 23, 2005
Revised: April 26, 2005
Accepted: April 30, 2005
Published online: November 21, 2005
Abstract

AIM: To investigate the influence of infliximab (Remicade) on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in rats.

METHODS: Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1: colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2–6. On the 7th d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were also measured.

RESULTS: Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared with the untreated ones was found (0.47±0.44, 1.09±0.86, 0.43±0.31 vs 18.73±10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4.

CONCLUSION: Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/kg BW.

Keywords: Experimental colitis, Infliximab, Inflammatory bowel disease, Tumor necrosis factor-alpha, Malondialdehyde, Ulcerative colitis