Altered inflammatory response and increased neurodegeneration in metallothionein I plus II deficient mice during experimental autoimmune encephalomyelitis

Metallothionein-I + II (MT-I + II) are antioxidant, neuroprotective protein s, and in this report we have examined their roles during experimental auto immune encephalomyelitis (EAE) by comparing MT-I + II-knock-out (MTKO) and wild-type mice. We herewith show that EAE susceptibility is higher in MTKO mice relatively to wild-type mice, and that the inflammatory responses elic ited by EAE in the central nervous system (CNS) are significantly altered b y MT-I + II deficiency. Thus, during EAE the MTKO mice showed increased mac rophage and T-lymphocytes infiltration in the CNS, while their reactive ast rogliosis was significantly decreased. In addition, the expression of the p roinflammatory cytokines interleukin-1 beta, interleukin-6, and tumor necro sis factor-alpha elicited by EAE was further increased in the MTKO mice, an d oxidative stress and apoptosis were also significantly increased in MTKO mice compared to normal mice. The present results strongly suggest that MT- I + II are major factors involved in the inflammatory response of the CNS d uring EAE and that they play a neuroprotective role in this scenario. (C) 2 001 Elsevier Science B.V. All rights reserved.