Effect of FTY720, a novel immunosuppressant, on adjuvant- and collagen-induced arthritis in rats.
The anti-arthritic effect of FTY720, 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride, a novel immunosuppressant which induces peripheral lymphocyte homing to peripheral lymph nodes, was compared with those of anti-rheumatic compounds, mizoribine and prednisolone in rat adjuvant-induced arthritis (AA) and collagen-induced arthritis (CIA). FTY720 at doses of 0.03-0.3 mg/kg, mizoribine at 3-30 mg/kg, and prednisolone at 1-10 mg/kg were orally administered to rats for 21 days from the day of inoculation with heat-killed Mycobacterium tuberculosis or type II collagen. Efficacy of FTY720 at 0.3 mg/kg was almost equal or higher as compared with those of mizoribine and prednisolone in both AA and CIA models. FTY720, but not mizoribine and prednisolone, decreased selectively lymphocyte counts in the peripheral blood in both models below the levels of the normal rats. Although FTY720 gave no other abnormal signs resulting in side effects, mizoribine was lethal to rats at 30 mg/kg and prednisolone inhibited body weight gain at 10 mg/kg, indicating that FTY720 has a wider margin of safety compared with these reference compounds. FTY720 also inhibited the production of anti-collagen antibody in CIA model, while neither mizoribine nor prednisolone did it. These results suggest that FTY720 is a promising compound for the treatment of arthritis with a unique profile.
Matsuura
M
M
Pharmacology, Drug Development Laboratories, Yoshitomi Pharmaceutical Industries Ltd, Koiwai 955, Yoshitomi-cho, Chikujo-gun, Fukuoka, Japan.matsuura_mamoru@yoshitomi.co.jp
Imayoshi
T
T
Okumoto
T
T
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D003094:Collagen / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use; D011409:Propylene Glycols / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012263:Ribonucleosides / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D012263:Ribonucleosides; C010052:mizoribine; D003094:Collagen; D011239:Prednisolone; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine