Reduction of spontaneous autoimmune diabetes in diabetes-prone BB rats with the novel immunosuppressant fusidic acid. Effect on T-cell proliferation and production of interferon-gamma.
Diabetes-prone (DP) BB rats spontaneously develop a hyperglycaemic condition which closely resembles human insulin-dependent diabetes mellitus (IDDM), both in terms of clinical and histological features. The incidence of IDDM was significantly reduced when these animals were treated with 2 or 4 mg fusidic acid (FA)/day i.m. from day 30 to day 120 of age. In addition, the mean insulitis score was significantly diminished in the animals treated with FA compared to both vehicle-treated and untreated controls. Finally, 2 mg/day of FA i.m. prevented cell proliferation and interferon-gamma secretion from peripheral blood mononuclear cells upon ex vivo stimulation with concanavalin A. The capacity of FA to substantially reduce the incidence of autoimmune diabetes in a well-known animal model of human IDDM supports previous observations regarding the immunosuppressive properties of FA and its potential use in the treatment of human autoimmune diabetes.
Nicoletti
F
F
Institute of Internal Medicine, Infectious Diseases and Immunopathology, University of Milan, Italy.
Di Marco
R
R
Morrone
S
S
Zaccone
P
P
Lembo
D
D
Grasso
S
S
Santoni
A
A
Meroni
P L
PL
Bendtzen
K
K
D000367:Age Factors; D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005672:Fusidic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood / Q000187:drug effects*; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB; D013601:T-Lymphocytes / Q000187:drug effects*
D003208:Concanavalin A; D005672:Fusidic Acid; D007371:Interferon-gamma