Multiple sclerosis is an inflammatory,
demyelinating disease of the CNS.
Metallothioneins-I+II are
antioxidant proteins induced in the CNS by immobilisation stress,
trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS
isoform metallothionein-III has been related to
Alzheimer's disease. We have analysed
metallothioneins-I-III expression in the CNS of mice with
experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of
interferon-gamma, a pro-inflammatory
cytokine, in the control of
metallothioneins expression during
experimental autoimmune encephalomyelitis in
interferon-gamma receptor knockout mice with two different genetic backgrounds: 129/Sv and C57BL/6x129/Sv. Mice with
experimental autoimmune encephalomyelitis showed a significant induction of
metallothioneins-I+II in the spinal cord white matter, and to a lower extent in the brain.
Interferon-gamma receptor knockout mice suffered from a more severe
experimental autoimmune encephalomyelitis, and interestingly showed a higher
metallothioneins-I+II induction in both white and grey matter of the spinal cord and in the brain. In contrast to the
metallothioneins-I+II
isoforms,
metallothionein-III expression remained essentially unaltered during
experimental autoimmune encephalomyelitis;
interferon-gamma receptor knockout mice showed an altered
metallothionein-III expression (a slight increase in the spinal cord white matter) only in the C57BL/6x129/Sv background.
Metallothioneins-I+II
proteins were prominent in areas of induced cellular infiltrates. Reactive astrocytes and activated monocytes/macrophages were the sources of
metallothioneins-I+II
proteins. From these results we suggest that
metallothioneins-I+II but not
metallothionein-III may play an important role during
experimental autoimmune encephalomyelitis, and indicate that the pro-inflammatory
cytokine interferon-gamma is unlikely an important factor in this response.