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PMID: 17437423 Published · ppublish English Journal Article

Therapeutic effect of a new immunosuppressive agent, everolimus, on interleukin-10 gene-deficient mice with colitis.

Clinical and experimental immunology ·Vol. 148 ·No. 2 ·2007-05-00 ·Pages 348-59

Matsuda C, Ito T, Song J, Mizushima T, Tamagawa H, Kai Y, Hamanaka Y, Inoue M, Nishida T, Matsuda H, Sawa Y

Abstract

A limited number of therapeutic strategies are currently available for patients with inflammatory bowel disease (IBD). In particular, the maintenance therapy after remission in Crohn's disease (CD) is not satisfactory and new approaches are needed. Interleukin-10 gene-deficient (IL-10-/-) mice, a well-characterized experimental model of CD, develop severe chronic colitis due to an aberrant Th1 immune response. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), a new immunosuppressive reagent, has been used successfully in animal models for heart, liver, lung and kidney transplantation. In the present study, we examined the efficacy of everolimus in the treatment of chronic colitis in an IL-10-/- mouse model. Everolimus was administered orally for a period of 4 weeks to IL-10-/- mice with clinical signs of colitis. The gross and histological appearances of the colon and the numbers, phenotype and cytokine production of lymphocytes were compared with these characteristics in a control group. The 4-week administration of everolimus resulted in a significant decrease in the severity of colitis, together with a significant reduction in the number of CD4+ T cells in the colonic lamina propria as well as IFN-gamma production in colonic lymphocytes. Everolimus treatment of established colitis in IL-10-/- mice ameliorated the colitis, probably as a result of decreasing the number of CD4+ T cells in the colonic mucosa and an associated reduction in IFN-gamma production.

MeSH Terms
Animals Body Weight/drug effects CD4-Positive T-Lymphocytes/drug effects Cells, Cultured Crohn Disease/drug therapy,immunology,pathology Cytokines/biosynthesis Disease Models, Animal Everolimus Female Immunosuppressive Agents/therapeutic use Interferon-gamma/biosynthesis Interleukin-10/deficiency Intestinal Mucosa/immunology Lymph Nodes/immunology Lymphocyte Count Male Mice Mice, Inbred C57BL Sirolimus/analogs & derivatives,therapeutic use Spleen/immunology T-Lymphocyte Subsets/immunology Treatment Outcome
Chemicals
Cytokines Immunosuppressive Agents Interleukin-10 Interferon-gamma Everolimus Sirolimus
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Matsuda C
Department of Surgery (E1), Osaka University Graduate School of Medicine, Japan.
Ito T
Song J
Mizushima T
Tamagawa H
Kai Y
Hamanaka Y
Inoue M
Nishida T
Matsuda H
Sawa Y
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Article Info
Journal
Clinical and experimental immunology
Abbr.
Clin Exp Immunol
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2007.03345.x
Published
2007-05-00
Pages
348-59
Language
English
Region
England
NLM ID
0057202
PMCID
PMC1868878
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1365-2249.2007.03345.x PMC Full Text View journal details
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