Tacrolimus (FK506) causes disease aggravation in models for inherited peripheral myelinopathies. Neurobiol Dis 2009 Feb;33(2):207-12
Date
11/26/2008Pubmed ID
19028581DOI
10.1016/j.nbd.2008.10.008Scopus ID
2-s2.0-58149490794 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Mice hetero- or homozygously deficient for myelin protein zero (P0+/-, P0-/- mice) are models for distinct forms of inherited de- or dysmyelinating neuropathies, respectively. P0+/- mice show a demyelinating neuropathy with a pathogenetic implication of CD8+ T-lymphocytes and macrophages, while P0-/- mice show dysmyelination with axonal loss. It was, therefore, of interest to treat both mutants with FK506 (Tacrolimus), an agent with immunosuppressive and neuroprotective properties. Treatment of P0+/- mice led to an aggravation of demyelination, without affecting nervous CD8+ T-lymphocytes, but reducing splenic CD4+ cells. Treatment of P0-/- mice resulted in a substantial increase of the dysmyelination-related axon loss. Treatment of wildtype mice did not cause pathological changes in peripheral nerves. Our study shows that FK506 may not be suitable for the treatment of the human nerve disorders. Furthermore, when used as an immunosuppressant, the drug may generate detrimental neurological side effects in patients with an additional hereditary neuropathy.
Author List
Ip CW, Kroner A, Kohl B, Wessig C, Martini RAuthor
Antje Kroner-Milsch MD, PhD Associate Professor in the Neurosurgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAxons
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Charcot-Marie-Tooth Disease
Demyelinating Diseases
Disease Models, Animal
Flow Cytometry
Immunohistochemistry
Immunosuppressive Agents
Macrophages
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Electron
Myelin P0 Protein
Myelin Sheath
Neural Conduction
Peripheral Nerves
Spleen
Tacrolimus
