Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis

Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Me tallothioneins-I+II are antioxidant proteins induced in the CNS by immobili sation stress, trauma or degenerative diseases which have been postulated t o play a neuroprotective role, while the CNS isoform metallothionein-III ha s been related to Alzheimer's disease. We have analysed metallothioneins-I- III expression in the CNS of mice with experimental autoimmune encephalomye litis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflarnmatory cytokine, in the control of metallothioneins expression d uring experimental autoimmune encephalomyelitis in interferon-gamma recepto r knockout mice with two different genetic backgrounds: 129/Sv and C57BL/6x 129/Sv. Mice with experimental autoimmune encephalomyelitis showed a significant in duction 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 interest ingly showed a higher metallothioneins-I+II induction in both white and gre y matter of the spinal cord and in the brain. In contrast to the metallothi oneins-I+II isoforms, metallothionein-III expression remained essentially u naltered 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/S v background. Metallothioneins-I+II proteins were prominent in areas of ind uced cellular infiltrates. Reactive astrocytes and activated monocytes/macr ophages were the sources of metallothioneins-I+II proteins. From these results we suggest that metallothioneins-I+II but not metallothi onein-III may play an important role during experimental autoimmune encepha lomyelitis, and indicate that the pro-inflammatory cytokine interferon-gamm a is unlikely an important factor in this response. (C) 2001 IBRO. Publishe d by Elsevier Science Ltd. All rights reserved.