Preventive effect of a new immunosuppressant FK-506 on insulitis and diabetes in non-obese diabetic mice.
We investigated the effect of an immunosuppressant FK-506 on histological change of islets, the onset of diabetes, and the change of spleen cell subsets in female non-obese diabetic mice. Mice administered intraperitoneally with FK-506 from 5 to 20 weeks of age showed marked suppression of mononuclear cell infiltration (insulitis) at 10 weeks of age. Among the subsets of the spleen cells, a significant decrease in the population of Thyl.2-positive T cells (pan-T), L3T4-positive T cells (mainly helper/inducer), and Lyt2-positive T cells (mainly suppressor/cytotoxic) was observed in FK-506-treated mice. Furthermore, glucose tolerance of the mice at 15 weeks of age was clearly improved. Cumulative incidence observed up to 40 weeks of age was 86% in control mice and 23% in FK-506-treated mice (p less than 0.01). These data indicate that FK-506 has a preventive effect on insulitis and diabetes by the suppression of cell-mediated autoimmunity in non-obese diabetic mice.
Second Department of Internal Medicine, Osaka University Medical School, Japan.
J
J
Miyagawa
K
K
Yamamoto
T
T
Hanafusa
N
N
Itoh
C
C
Nakagawa
A
A
Otsuka
H
H
Katsura
K
K
Yamagata
A
A
Miyazaki
N
N
Kono
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000628:therapy*; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051379:Mice; D008820:Mice, Obese; D010179:Pancreas / Q000276:immunology / Q000473:pathology*; D010182:Pancreatic Diseases / Q000473:pathology / Q000628:therapy*; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D016559:Tacrolimus