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Anti-IL-6-receptor antibody promotes repair of spinal cord injury by inducing microglia-dominant inflammation.
Mukaino, Masahiko; Nakamura, Masaya; Yamada, Osamu; Okada, Seiji; Morikawa, Satoru; Renault-Mihara, Francois; Iwanami, Akio; Ikegami, Takeshi; Ohsugi, Yoshiyuki; Tsuji, Osahiko; Katoh, Hiroyuki; Matsuzaki, Yumi; Toyama, Yoshiaki; Liu, Meigen; Okano, Hideyuki.
Afiliação
  • Mukaino M; Department of Rehabilitation Medicine, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
Exp Neurol ; 224(2): 403-14, 2010 Aug.
Article em En | MEDLINE | ID: mdl-20478301
ABSTRACT
We previously reported the beneficial effect of administering an anti-mouse IL-6 receptor antibody (MR16-1) immediately after spinal cord injury (SCI). The purpose of our present study was to clarify the mechanism underlying how MR16-1 improves motor function after SCI. Quantitative analyses of inflammatory cells using flow cytometry, and immunohistochemistry with bone marrow-chimeric mice generated by transplanting genetically marked purified hematopoietic stem cells, revealed that MR16-1 dramatically switched the central player in the post-traumatic inflammation, from hematogenous macrophages to resident microglia. This change was accompanied by alterations in the expression of relevant cytokines within the injured spinal cord; the expression of recruiting chemokines including CCL2, CCL5, and CXCL10 was decreased, while that of Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF), a known mitogen for microglia, was increased. We also showed that the resident microglia expressed higher levels of phagocytic markers than the hematogenous macrophages. Consistent with these findings, we observed significantly decreased tissue damage and reduced levels of myelin debris and Nogo-A, the axonal growth inhibitor, by MR16-1 treatment. Moreover, we observed increased axonal regeneration and/or sprouting in the MR16-1-treated mice. Our findings indicate that the functional improvement elicited by MR16-1 involves microglial functions, and provide new insights into the role of IL-6 signaling in the pathology of SCI.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismos da Medula Espinal / Microglia / Receptores de Interleucina-6 / Anticorpos Monoclonais Limite: Animals Idioma: En Revista: Exp Neurol Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismos da Medula Espinal / Microglia / Receptores de Interleucina-6 / Anticorpos Monoclonais Limite: Animals Idioma: En Revista: Exp Neurol Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Japão