Effect of FTY720, a novel immunosuppressant, on adjuvant-induced arthritis in rats.
OBJECTIVE
Anti-arthritic effect of FTY720, a novel immunosuppressant, was compared with those of immunosuppressants cyclosporin A and tacrolimus in adjuvant-induced arthritis in rats.


METHODS
Male LEW rats.


METHODS
FTY720 (0.03-0.3 mg/kg), cyclosporin A (1-10 mg/kg) or tacrolimus (0.3-3 mg/kg) were orally administered to rats for 21 days beginning on the day (day 0) of adjuvant inoculation. In addition, the anti-arthritic effect of FTY720 (0.3 mg/kg) and cyclosporin A (10 mg/kg) were evaluated by administration to animals for 5 consecutive days (days 2-6, 6-10, and 10-14).


METHODS
Adjuvant-induced arthritis was produced by intradermal injection of 0.5 mg heat-killed Mycobacterium tuberculosis. Hindpaw edema was measured plethysmographically. The day of arthritis onset was determined macroscopically. Bone degradation was determined by radiography. Peripheral blood leukocytes were classified microscopically.


RESULTS
All test compounds inhibited the incidence of arthritis, hindpaw edema and bone destruction. In addition, FTY720 but not cyclosporin A or tacrolimus markedly decreased the number of peripheral blood lymphocytes. FTY720 treatment on days 6 to 10 inhibited the bone destruction and hindpaw edema.


CONCLUSIONS
These results suggest that the anti-arthritic effect of FTY720 in this adjuvant-induced arthritic model was more potent than those of cyclosporin A and tacrolimus. FTY720 administered on days 6 to 10 showed the inhibitory effect on the bone destruction and hindpaw edema. FTY720 may be effective in the treatment of rheumatoid arthritis.
Matsuura
M
M
Drug Development Laboratories, Welfide Corporation, Chikujo-gun, Fukuoka, Japan. matsuura_mamoru@welfide.co.jp
Imayoshi
T
T
Chiba
K
K
Okumoto
T
T
D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004487:Edema / Q000517:prevention & control; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007958:Leukocyte Count; D008214:Lymphocytes; D008297:Male; D009000:Monocytes; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009504:Neutrophils; D010014:Osteolysis / Q000517:prevention & control; D011409:Propylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013110:Sphingosine / Q000031:analogs & derivatives; D016559:Tacrolimus / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D016559:Tacrolimus