Favorable response to subcutaneous administration of infliximab in rats with experimental colitis.
OBJECTIVE
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 7(th) 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-alpha) 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-alpha 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.


CONCLUSIONS
Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-alpha 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-alpha 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.
Triantafillidis
John K
JK
Department of Gastroenterology, Saint Panteleimon General State Hospital, Nicea, Greece. jkt@panafonet.gr
Papalois
Apostolos E
AE
Parasi
Aikaterini
A
Anagnostakis
Emmanuel
E
Burnazos
Stavros
S
Gikas
Aristofanis
A
Merikas
Emmanuel G
EG
Douzinas
Emmanuel
E
Karagianni
Maria
M
Sotiriou
Helen
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D000069285:Infliximab; D007279:Injections, Subcutaneous; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D000069285:Infliximab