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 proteins, and in this report we have examined their roles during experimental autoimmune 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 elicited by EAE in the central nervous system (CNS) are significantly altered by MT-I + II deficiency. Thus, during EAE the MTKO mice showed increased macrophage and T-lymphocytes infiltration in the CNS, while their reactive astrogliosis was significantly decreased. In addition, the expression of the proinflammatory cytokines interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha elicited by EAE was further increased in the MTKO mice, and 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 during EAE and that they play a neuroprotective role in this scenario. (C) 2001 Elsevier Science B.V. All rights reserved.