Abstract
Oral tolerance is a recognized procedure for induction of antigen-specific peripheral immune hyporesponsiveness. Recently, it has been shown that oral tolerance can be used to prevent experimental colitis. The aim of this study was to test whether induction of oral tolerance toward proteins extracted from inflammatory and noninflammatory colons can alleviate preexisting experimental colitis. Colitis was induced in BALB/c mice by intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS-induced colitis or normal colons, before, or 7 days after colitis was induced. Standard clinical, macroscopic, and microscopic scores were used for colitis assessment. Serum interferon γ (IFNγ) and interleukin (IL)4 levels were measured by enzyme-linked immunosorbent assay. Feeding of colitis- or normal colon-extracted proteins before, or following colitis induction, ameliorated colonic inflammation as shown by decreased diarrhea, increased body weight, reduction of colonic ulcerations, intestinal and peritoneal adhesions, wall thickness, and edema. Histological parameters for colitis were markedly improved in tolerized animals, and there was a significant reduction in inflammatory response and mucosal ulcerations. Tolerized mice developed an increase in IL4 and a decrease in IFNγ serum levels. The results show that induction of oral tolerance to colitis- or normal colon-extracted proteins down-regulated preexisting anticolon immune response, thereby ameliorating experimental colitis. Tolerance induction was mediated via a shift from a proinflammatory T helper (Th)1 to an anti-inflammatory Th2 immune response.
Footnotes
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Send reprint requests to: Yaron Ilan, M.D., Liver Unit, Division of Medicine, Hadassah University Hospital, P.O. 12000, Jerusalem, Israel IL-91120. E-mail:Ilan{at}hadassah.org.il
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This work was supported in part by the following grants: Hadasit-Yissum; a grant from ENZO Biochem Inc., New York, NY; Israel Academy of Sciences Grant; and The Roaman-Epstein Liver Research Foundation (to Y.I.).
- Abbreviations:
- IBD
- inflammatory bowel disease
- Th
- T helper
- IFNγ
- interferon γ
- IL
- interleukin
- TNBS
- 2,4,6-trinitrobenzenesulfonic acid
- CEP
- colitis-extracted protein
- NCEP
- normal colon extracted protein
- BSA
- bovine serum albumin
- Received September 19, 2000.
- Accepted January 31, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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