Blockade of interleukin-6 effects on cytokine profiles and macrophage activation after spinal cord injury in mice

Alexander Rodriguez Guerrero, Kenzo Uchida, Hideaki Nakajima, Shuji Watanabe, Masaya Nakamura, Seiji Okada, William E.B. Johnson, Hisatoshi Baba

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)

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.

Original languageEnglish
Title of host publicationNeuroprotection and regeneration of the spinal cord
EditorsKenzo Uchida, Masaya Nakamura, Hiroshi Ozawa, et al
Place of PublicationTokyo (JP)
PublisherSpringer
Pages203-212
Number of pages10
ISBN (Electronic)978-4-431-54502-6
ISBN (Print)978-4-431-54501-9
DOIs
Publication statusPublished - 31 Jan 2014

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Macrophage Activation
Spinal Cord Injuries
Interleukin-6 Receptors
Interleukin-6
Cytokines
Macrophages
Arginase
Thoracic Injuries
Acute-Phase Reaction
Antibodies
Regeneration
Up-Regulation
Down-Regulation
Monoclonal Antibodies
Wounds and Injuries

Keywords

  • alternatively activated macrophage
  • interleukin (IL)-6/IL-6 receptor (R)
  • spinal cord injury
  • T helper (Th) cytokine

Cite this

Rodriguez Guerrero, A., Uchida, K., Nakajima, H., Watanabe, S., Nakamura, M., Okada, S., ... Baba, H. (2014). Blockade of interleukin-6 effects on cytokine profiles and macrophage activation after spinal cord injury in mice. In K. Uchida, M. Nakamura, H. Ozawa, & et al (Eds.), Neuroprotection and regeneration of the spinal cord (pp. 203-212). Tokyo (JP): Springer. https://doi.org/10.1007/978-4-431-54502-6_17
Rodriguez Guerrero, Alexander ; Uchida, Kenzo ; Nakajima, Hideaki ; Watanabe, Shuji ; Nakamura, Masaya ; Okada, Seiji ; Johnson, William E.B. ; Baba, Hisatoshi. / Blockade of interleukin-6 effects on cytokine profiles and macrophage activation after spinal cord injury in mice. Neuroprotection and regeneration of the spinal cord. editor / Kenzo Uchida ; Masaya Nakamura ; Hiroshi Ozawa ; et al. Tokyo (JP) : Springer, 2014. pp. 203-212
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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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Rodriguez Guerrero, A, Uchida, K, Nakajima, H, Watanabe, S, Nakamura, M, Okada, S, Johnson, WEB & Baba, H 2014, Blockade of interleukin-6 effects on cytokine profiles and macrophage activation after spinal cord injury in mice. in K Uchida, M Nakamura, H Ozawa & et al (eds), Neuroprotection and regeneration of the spinal cord. Springer, Tokyo (JP), pp. 203-212. https://doi.org/10.1007/978-4-431-54502-6_17

Blockade of interleukin-6 effects on cytokine profiles and macrophage activation after spinal cord injury in mice. / Rodriguez Guerrero, Alexander; Uchida, Kenzo; Nakajima, Hideaki; Watanabe, Shuji; Nakamura, Masaya; Okada, Seiji; Johnson, William E.B.; Baba, Hisatoshi.

Neuroprotection and regeneration of the spinal cord. ed. / Kenzo Uchida; Masaya Nakamura; Hiroshi Ozawa; et al. Tokyo (JP) : Springer, 2014. p. 203-212.

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)

TY - CHAP

T1 - Blockade of interleukin-6 effects on cytokine profiles and macrophage activation after spinal cord injury in mice

AU - Rodriguez Guerrero, Alexander

AU - Uchida, Kenzo

AU - Nakajima, Hideaki

AU - Watanabe, Shuji

AU - Nakamura, Masaya

AU - Okada, Seiji

AU - Johnson, William E.B.

AU - Baba, Hisatoshi

PY - 2014/1/31

Y1 - 2014/1/31

N2 - 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.

AB - 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.

KW - alternatively activated macrophage

KW - interleukin (IL)-6/IL-6 receptor (R)

KW - spinal cord injury

KW - T helper (Th) cytokine

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UR - http://link.springer.com/chapter/10.1007%2F978-4-431-54502-6_17

U2 - 10.1007/978-4-431-54502-6_17

DO - 10.1007/978-4-431-54502-6_17

M3 - Chapter (peer-reviewed)

SN - 978-4-431-54501-9

SP - 203

EP - 212

BT - Neuroprotection and regeneration of the spinal cord

A2 - Uchida, Kenzo

A2 - Nakamura, Masaya

A2 - Ozawa, Hiroshi

A2 - et al,

PB - Springer

CY - Tokyo (JP)

ER -

Rodriguez Guerrero A, Uchida K, Nakajima H, Watanabe S, Nakamura M, Okada S et al. Blockade of interleukin-6 effects on cytokine profiles and macrophage activation after spinal cord injury in mice. In Uchida K, Nakamura M, Ozawa H, et al, editors, Neuroprotection and regeneration of the spinal cord. Tokyo (JP): Springer. 2014. p. 203-212 https://doi.org/10.1007/978-4-431-54502-6_17