Deferiprone, an orally deliverable iron chelator, ameliorates experimental autoimmune encephalomyelitis.
The iron chelator, Desferal, suppressed disease activity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), and it has been tested in pilot trials for MS. The administration regimen of Desferal is cumbersome and prone to complications. Orally-deliverable, iron chelators have been developed that circumvent these difficulties, and the objective of this study was to test an oral chelator in EAE. SJL mice with active EAE were randomly assigned to receive deferiprone (150 mg/kg) or vehicle (water) 2x/day via gavage. EAE mice given deferiprone had significantly less disease activity and lower levels of inflammatory cell infiltrates (revealed by H&E staining) than EAE mice administered vehicle. T-cell infiltration, assessed by anti-CD3 immunohistochemical staining, also was reduced, although not significantly. Splenocytes cultured from naïve SJL mice were stimulated with anti-CD3 and anti-CD28 with or without 250 microM deferiprone. While approximately 39% of costimulated splenocytes without deferiprone underwent division, only approximately 2.8% of costimulated splenocytes with deferiprone divided and the latter cells were only 53% as viable as the former. Deferiprone had no effect on proliferation or viability of cells that were not costimulated. In summary, deferiprone effectively suppressed active EAE disease and it inhibited T-cell function.
Mitchell
K M
KM
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Dotson
A L
AL
Cool
K M
KM
Chakrabarty
A
A
Benedict
S H
SH
LeVine
S M
SM
D000284:Administration, Oral; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D000077543:Deferiprone; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D007502:Iron Chelating Agents / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011728:Pyridones / Q000494:pharmacology*; D012720:Severity of Illness Index; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone