The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice.
To evaluate the therapeutic effects of the new synthetic sphingosine-1-phosphate (S1P) receptor modulator, FTY720, we investigated how FTY720 affects the development of dextran sulfate sodium (DSS)-induced colitis and CD4+CD62L+ T cell transfer colitis. BALB/c mice were fed a chow containing 3.5% (wt/wt) DSS to induce colitis. The CD4+CD62L+ T cell transfer colitis was induced by an intraperitoneal injection of CD4+CD62L+ spleen T cells into recipient CB17 SCID mice. The FTY720 was administered by lavage at a dose of 0.3 mg/kg/day. FTY720 was effective in preventing the body weight loss in the DSS-colitis model and the CD4+CD62L+ T cell transfer model. The disease activity index, histological colitis score, and MPO activity were all significantly lower in FTY720-treated mice than in the non-treated mice. Microscopically, mucosal edema, cellular infiltration and epithelial disruption were much more moderate in the FTY720-treated mice than in the non-treated mice. In both colitis models, FTY720 prevented the infiltration of CD4+ T cells into the inflamed colonic lamina propria. In conclusion, the development of DSS-colitis and CD4+CD62L+ T cell transfer colitis were significantly attenuated by FTY720. Since FTY720 is an immunosuppressive product that does not modulate T cell functions, it could be useful in the treatment of IBD patients.
Deguchi
Yasuyuki
Y
Department of Internal Medicine, Shiga University of Medical Science, Otsu 520-2192, Japan.
Andoh
Akira
A
Yagi
Yuki
Y
Bamba
Shigeki
S
Inatomi
Osamu
O
Tsujikawa
Tomoyuki
T
Fujiyama
Yoshihide
Y
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D017690:Cell Transplantation; D003092:Colitis / Q000517:prevention & control*; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015212:Inflammatory Bowel Diseases / Q000517:prevention & control / Q000628:therapy; D019041:L-Selectin / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011409:Propylene Glycols / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D019041:L-Selectin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine