Effect of FTY720, a novel immunosuppressant, on adjuvant-induced arthritis in rats.

Abstract

OBJECTIVE AND DESIGN:

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

MATERIAL:

Male LEW rats.

TREATMENT:

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.

CONCLUSION:

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.

• Authors: M Matsuura, T Imayoshi, K Chiba, T Okumoto
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 49 Issue 8 Pg. 404-10 (Aug 2000) ISSN: 1023-3830 [Print] Switzerland
• PMID: 11028757 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Immunosuppressive Agents
• Propylene Glycols
• Cyclosporine
• Fingolimod Hydrochloride
• Sphingosine
• Tacrolimus

Topics

• Animals
• Arthritis, Experimental (blood, immunology, prevention & control)
• Cyclosporine (administration & dosage, therapeutic use)
• Edema (prevention & control)
• Fingolimod Hydrochloride
• Immunosuppressive Agents (therapeutic use)
• Leukocyte Count
• Lymphocytes
• Male
• Monocytes
• Mycobacterium tuberculosis (immunology)
• Neutrophils
• Osteolysis (prevention & control)
• Propylene Glycols (administration & dosage, therapeutic use)
• Rats
• Rats, Inbred Lew
• Sphingosine (analogs & derivatives)
• Tacrolimus (therapeutic use)