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

doi: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

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

^*Corresponding author for this work

Research output: Chapter in Book/Published conference output › Chapter (peer-reviewed) › peer-review

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 language	English
Title of host publication	Neuroprotection and regeneration of the spinal cord
Editors	Kenzo Uchida, Masaya Nakamura, Hiroshi Ozawa, et al
Place of Publication	Tokyo (JP)
Publisher	Springer
Pages	203-212
Number of pages	10
ISBN (Electronic)	978-4-431-54502-6
ISBN (Print)	978-4-431-54501-9
DOIs	https://doi.org/10.1007/978-4-431-54502-6_17
Publication status	Published - 31 Jan 2014

Keywords

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

Access to Document

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

Cite this

Rodriguez Guerrero, A., Uchida, K., Nakajima, H., Watanabe, S., Nakamura, M., Okada, S., Johnson, W. E. B., & 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). Springer. https://doi.org/10.1007/978-4-431-54502-6_17

@inbook{9de7bf43b12c45beb701ff44f324b417,

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

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.",

keywords = "alternatively activated macrophage, interleukin (IL)-6/IL-6 receptor (R), spinal cord injury, T helper (Th) cytokine",

author = "{Rodriguez Guerrero}, Alexander and Kenzo Uchida and Hideaki Nakajima and Shuji Watanabe and Masaya Nakamura and Seiji Okada and Johnson, {William E.B.} and Hisatoshi Baba",

year = "2014",

month = jan,

day = "31",

doi = "10.1007/978-4-431-54502-6_17",

language = "English",

isbn = "978-4-431-54501-9",

pages = "203--212",

editor = "Kenzo Uchida and Masaya Nakamura and Hiroshi Ozawa and {et al}",

booktitle = "Neuroprotection and regeneration of the spinal cord",

publisher = "Springer",

address = "Germany",

}

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 et al.
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/Published conference output › Chapter (peer-reviewed) › peer-review

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

UR - http://www.scopus.com/inward/record.url?scp=84930707556&partnerID=8YFLogxK

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)

AN - SCOPUS:84930707556

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 doi: 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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Microarray analysis of expression of cell death-associated genes in spinal cord cells with cyclic tensile strain

Cite this