Experimental treatment of autoimmune MRL-lpr/lpr mice with immunosuppressive compound FK506.
A newly developed immunosuppressive drug, FK506 (Fujisawa, Japan) is known to inhibit T-cell immunity. We have evaluated the action of this compound in MRL/lpr mice which develop a severe autoimmune disease. Eight-week-old female MRL/lpr of mice were treated subcutaneously with 2 mg/kg (high dose), 0.8 mg/kg (medium dose), 0.2 mg/kg (low dose) or solvent only (control) six times per week. Survival times of the mice were prolonged in the medium and the high dose treatment groups. The lymph node swelling was dramatically prevented with the high dose treatment. The increasing footpad swelling seemed to be also suppressed with the treatment. FACS analyses of the spleen cells revealed that FK506 reduced the percentage of double negative T cells (Thy-1.2+, Lyt-2-, L3T4-). Serological studies showed that anti-ssDNA and anti-dsDNA activities were significantly reduced by the high dose treatment, which is different from recent findings with Cyclosporine A. The high dose treatment also suppressed the total amount of IgG, even though the IgG concentration was rather increased by the medium dose treatment. Decreased proteinuria as well as pathological evaluations of the kidneys and lungs indicated that there were marked ameliorations in these organs with the treatment. These results suggest that FK506 could be potentially used for the treatment of autoimmune diseases.
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
K
K
Yamamoto
A
A
Mori
T
T
Nakahama
M
M
Ito
H
H
Okudaira
T
T
Miyamoto
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000517:prevention & control; D001327:Autoimmune Diseases / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000517:prevention & control; D008206:Lymphatic Diseases / Q000517:prevention & control; D051379:Mice; D008817:Mice, Mutant Strains; D011658:Pulmonary Fibrosis / Q000517:prevention & control; D013601:T-Lymphocytes / Q000187:drug effects; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016559:Tacrolimus