Treatment with rapamycin ameliorates clinical and histological signs of protracted relapsing experimental allergic encephalomyelitis in Dark Agouti rats and induces expansion of peripheral CD4+CD25+Foxp3+ regulatory T cells.
We have presently evaluated the effects of the immunomodulatory drug rapamycin on the course of protracted relapsing experimental allergic encephalomyelitis (PR-EAE) in Dark Agouti (DA) rats, which serves as a preclinical model of multiple sclerosis. The data show that the oral administration of rapamycin at 3 mg/kg for 28 consecutive days significantly ameliorated the course of PR-EAE in DA rats. The rats that received the medication had significantly lower clinical cumulative scores and shorter duration of the disease than did the control rats treated with the vehicle. The milder course of the disease was associated with a reduction of the histopathological signs associated to EAE: increased percentage of splenic CD4+CD25 + Foxp3+ Tregs and concomitant reduction of splenic CD8+T cells. These data suggest that rapamycin has pharmacological potential worthy of consideration in the treatment of MS patients.
Donia
Marco
M
Department of Biomedical Sciences, School of Medicine, University of Catania, Catania, Italy.
Mangano
Katia
K
Amoroso
Alfredo
A
Mazzarino
Maria Clorinda
MC
Imbesi
Rosa
R
Castrogiovanni
Paola
P
Coco
Marinella
M
Meroni
Pierluigi
P
Nicoletti
Ferdinando
F
D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D007166:Immunosuppressive Agents; D020123:Sirolimus