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Blockade of Interleukin-6 Effects on Cytokine Profiles and Macrophage Activation After Spinal Cord Injury in Mice

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Abstract

The objective of this study was to clarify the effects of a temporal blockade of IL-6/IL-6 receptor (IL-6R) engagement, using an anti-mouse IL-6R monoclonal antibody (MR16-1), on macrophage activation and the inflammatory response in the acute phase after spinal cord injury (SCI) in mice. MR16-1 antibodies versus isotype control antibodies or saline alone was administered immediately after thoracic SCI in mice. MR16-1-treated group samples showed increased neuronal regeneration and locomotor recovery compared with controls. Immunoblot analysis of the MR16-1-treated samples identified downregulation of Th1 and upregulation of Th2 cytokines. MR16-1 treatment promoted arginase-1-positive, CD206-positive M2 macrophages, with preferential localization of these cells at the injury site and enhanced positivity for Mac-2 and Mac-3, suggestive of increased phagocytic behavior. The results suggest that temporal blockade of IL-6 signaling after SCI abrogates damaging inflammatory activity and promotes functional recovery by promoting the formation of alternatively activated M2 macrophages.

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Acknowledgment

 This work was supported in part by Grants-in-Aid to HN, KU, and HB for General Scientific Research of the Ministry of Education, Science and Culture of Japan (grants numbers B19791023, C21591895, C21791389, B22390287, and B23791631).

Conflict of Interest  All authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan

    Alexander Rodriguez Guerrero

  2. Service of Neurosurgery, Hospital Nacional Rosales, University of El Salvador, San Salvador, El Salvador

    Alexander Rodriguez Guerrero

  3. Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Matsuoka Shimoaizuki 23-3, Eiheiji, Fukui, 910-1193, Japan

    Kenzo Uchida, Hideaki Nakajima, Shuji Watanabe & Hisatoshi Baba

  4. Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan

    Masaya Nakamura

  5. Department of Advance Medical Initiatives, Orthopedics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Seiji Okada

  6. Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK

    William E. B. Johnson

Authors
  1. Alexander Rodriguez Guerrero
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  2. Kenzo Uchida
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  3. Hideaki Nakajima
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  4. Shuji Watanabe
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  5. Masaya Nakamura
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  6. Seiji Okada
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  7. William E. B. Johnson
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  8. Hisatoshi Baba
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Corresponding author

Correspondence to Kenzo Uchida .

Editor information

Editors and Affiliations

  1. Dept of Orthop & Rehabilit Med, University of Fukui Faculty of Medical Sciences, Yoshida-gun, Fukui, Japan

    Kenzo Uchida

  2. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Tokyo, Japan

    Masaya Nakamura

  3. Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Hiroshi Ozawa

  4. Department of Orthopedic Surgery, Faculty of Medicine The University of Tokushima, Tokushima, Tokushima, Japan

    Shinsuke Katoh

  5. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Tokyo, Japan

    Yoshiaki Toyama

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© 2014 Springer Japan

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Guerrero, A.R. et al. (2014). Blockade of Interleukin-6 Effects on Cytokine Profiles and Macrophage Activation After Spinal Cord Injury in Mice. In: Uchida, K., Nakamura, M., Ozawa, H., Katoh, S., Toyama, Y. (eds) Neuroprotection and Regeneration of the Spinal Cord. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54502-6_17

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  • DOI: https://doi.org/10.1007/978-4-431-54502-6_17

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  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54501-9

  • Online ISBN: 978-4-431-54502-6

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