Abstract | BACKGROUND: METHODS: Chronic colitis was established in Balb/c mice after four feeding cycles of dextran sodium sulfate. Because leukocyte recruitment to sites of intestinal inflammation is crucial for the development of chronic colitis, intravital microscopy was used to study the effect of rapamycin and CsA on leukocyte-endothelium interactions and leukocyte extravasation. To assess the degree of colitis, histological sections were evaluated. RESULTS: Both rapamycin and cyclosporine effectively reduced leukocyte sticking (>60%) in submucosal venules, as compared to controls. Furthermore, rapamycin, but not CsA, reduced (>35%) leukocyte extravasation in the mucosa. Both rapamycin and CsA treatments significantly improved the histologic inflammation score. CONCLUSION: Our in vivo results demonstrate that rapamycin reduces leukocyte sticking and extravasation during chronic colitis induction and proves to be as effective as CsA at reducing experimental chronic colitis. These results support the use of rapamycin in clinical trials to avoid serious side effects of CsA therapy in chronic colitis patients.
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Authors | Stefan Farkas, Matthias Hornung, Christine Sattler, Markus Guba, Markus Steinbauer, Matthias Anthuber, Hans Herfarth, Hans J Schlitt, Edward K Geissler |
Journal | International journal of colorectal disease
(Int J Colorectal Dis)
Vol. 21
Issue 8
Pg. 747-53
(Dec 2006)
ISSN: 0179-1958 [Print] Germany |
PMID | 16228179
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Immunosuppressive Agents
- Cyclosporine
- Dextran Sulfate
- Sirolimus
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Topics |
- Animals
- Cell Adhesion
(drug effects)
- Cell Communication
(drug effects)
- Cell Movement
(drug effects)
- Chronic Disease
- Colitis
(blood, chemically induced, prevention & control)
- Cyclosporine
(pharmacology)
- Dextran Sulfate
- Disease Models, Animal
- Endothelial Cells
(drug effects)
- Female
- Immunosuppressive Agents
(pharmacology)
- Intestinal Mucosa
(cytology, drug effects)
- Leukocyte Rolling
(drug effects)
- Leukocytes
(drug effects)
- Mice
- Mice, Inbred BALB C
- Predictive Value of Tests
- Sirolimus
(pharmacology)
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