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Immunological Characterization of Relapsed-Colitis Modelby Trinitrobenzene Sulfonic Acid in Rats

Hiroyuki ITO1,Toshihiko KATO1,Iori KAWATA1,Hiroyuki BITO1,Hirokazu KAWAGISHI1
Shuhachi KIRIYAMA2,and Tatsuya MORITA1*

1Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University
2Luminacoid Laboratory

 We established trinitrobenzene sulfonic acid (TNBS)-relapsed colitis and investigated its immunological properties in rats. Initial colitis was induced in F344, Wistar or Sprague-Dawley (SD) rats by the intracolonic administration of TNBS/50% ethanol. Five weeks after the induction, rats were re-administrated TNBS/saline by intravenous or intraperitoneal routes.
Relapsed colitis was the most apparent in SD rats receiving intravenous TNBS as assessed by colonic myeloperoxidase (MPO) activity. Biochemical and immunohistological comparisons were made between acute (8 days after intracolonic TNBS administration) and relapsed colitis (after intravenous TNBS re-administration) in SD rats. The acute colitis was accompanied by a severe increase in MPO activity and an accumulation of granulocytes, while the MPO activity in relapsed colitis was modest but the accumulation of T cells was apparent. In SD rats just before and after TNBS re-administration, serum IgG1 concentrations were greater than in those not given TNBS at all, while serum IgG2a concentrations were comparable among the groups. Both Th1 (IFN-γ and IL-2) and Th2 (IL-4, IL-6 and IL-10) cytokines in the colonic lamina propria CD4+ T cells were significantly greater in rats after relapse than in those not given TNBS at all and those before relapse. These results suggest that the current colitis model is accompanied by Th1 and Th2 driven immune activation.


Key words: Inflammatory bowel disease, TNBS-relapsed colitis, Myeloperoxidase, CD4+T cells, Cytokine profile, Rat


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