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

作者: Alexander Rodriguez Guerrero , Kenzo Uchida , Hideaki Nakajima , Shuji Watanabe , Masaya Nakamura

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

关键词:

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

参考文章(29)
T Kishimoto, S Akira, M Narazaki, T Taga, Interleukin-6 family of cytokines and gp130. Blood. ,vol. 86, pp. 1243- 1254 ,(1995) , 10.1182/BLOOD.V86.4.1243.BLOODJOURNAL8641243
Yonit Bomstein, Jonathan B. Marder, Karen Vitner, Igor Smirnov, Galit Lisaey, Oleg Butovsky, Valentin Fulga, Eti Yoles, Features of skin-coincubated macrophages that promote recovery from spinal cord injury. Journal of Neuroimmunology. ,vol. 142, pp. 10- 16 ,(2003) , 10.1016/S0165-5728(03)00260-1
Hideyuki Okano, Seiji Okada, Masaya Nakamura, Yoshiaki Toyama, Neural stem cells and regeneration of injured spinal cord. Kidney International. ,vol. 68, pp. 1927- 1931 ,(2005) , 10.1111/J.1523-1755.2005.00621.X
E. H. S. Choy, D. A. Isenberg, T. Garrood, S. Farrow, Y. Ioannou, H. Bird, N. Cheung, B. Williams, B. Hazleman, R. Price, K. Yoshizaki, N. Nishimoto, T. Kishimoto, G. S. Panayi, Therapeutic benefit of blocking interleukin‐6 activity with an anti–interleukin‐6 receptor monoclonal antibody in rheumatoid arthritis: A randomized, double‐blind, placebo‐controlled, dose‐escalation trial Arthritis & Rheumatism. ,vol. 46, pp. 3143- 3150 ,(2002) , 10.1002/ART.10623
Samuel David, Antje Kroner, Repertoire of microglial and macrophage responses after spinal cord injury Nature Reviews Neuroscience. ,vol. 12, pp. 388- 399 ,(2011) , 10.1038/NRN3053
D. L. Gruol, T. E. Nelson, Physiological and pathological roles of interleukin-6 in the central nervous system. Molecular Neurobiology. ,vol. 15, pp. 307- 339 ,(1997) , 10.1007/BF02740665
S. Okada, M. Nakamura, Y. Mikami, T. Shimazaki, M. Mihara, Y. Ohsugi, Y. Iwamoto, K. Yoshizaki, T. Kishimoto, Y. Toyama, H. Okano, Blockade of Interleukin-6 Receptor Suppresses Reactive Astrogliosis and Ameliorates Functional Recovery in Experimental Spinal Cord Injury Journal of Neuroscience Research. ,vol. 76, pp. 265- 276 ,(2004) , 10.1002/JNR.20044
Frédéric Ethuin, Bénédicte Gérard, Jamel E Benna, Anne Boutten, Marie-Anne Gougereot-Pocidalo, Laurent Jacob, Sylvie Chollet-Martin, Human neutrophils produce interferon gamma upon stimulation by interleukin-12 Laboratory Investigation. ,vol. 84, pp. 1363- 1371 ,(2004) , 10.1038/LABINVEST.3700148
J. Ma, T. Chen, J. Mandelin, A. Ceponis, N. E. Miller, M. Hukkanen, G. F. Ma, Y. T. Konttinen, Regulation of Macrophage Activation Cellular and Molecular Life Sciences. ,vol. 60, pp. 2334- 2346 ,(2003) , 10.1007/S00018-003-3020-0