TY - CHAP
T1 - Blockade of interleukin-6 effects on cytokine profiles and macrophage activation after spinal cord injury in mice
AU - Guerrero, Alexander Rodriguez
AU - Uchida, Kenzo
AU - Nakajima, Hideaki
AU - Watanabe, Shuji
AU - Nakamura, Masaya
AU - Okada, Seiji
AU - Johnson, William E.B.
AU - Baba, Hisatoshi
N1 - Publisher Copyright:
© 2014 Springer Japan. All rights reserved.
PY - 2014/11/1
Y1 - 2014/11/1
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
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U2 - 10.1007/978-4-431-54502-6_17
DO - 10.1007/978-4-431-54502-6_17
M3 - Chapter
AN - SCOPUS:84930707556
SN - 4431545018
SN - 9784431545019
VL - 9784431545026
SP - 203
EP - 212
BT - Neuroprotection and Regeneration of the Spinal Cord
PB - Springer Japan
ER -