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Potent pro-inflammatory actions of leukemia inhibitory factor in the spinal cord of the adult mouse

Kerr, Bradley J. and Patterson, Paul H. (2004) Potent pro-inflammatory actions of leukemia inhibitory factor in the spinal cord of the adult mouse. Experimental Neurology, 188 (2). pp. 391-407. ISSN 0014-4886. doi:10.1016/j.expneurol.2004.04.012.

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Injury in the peripheral or central nervous systems causes a significant rise in the levels of the pleiotropic cytokine leukemia inhibitory factor (LIF). This increase influences cell survival, reactive gliosis and inflammatory responses. Since prior work has focused primarily on peripheral nerve and brain, little is known about the role of LIF in the spinal cord injury response. We address this issue by examining the effects of injury in the LIF knockout (KO) mouse, as well as using an adenoviral vector to over-express LIF in the spinal cord of adult mice. We find that LIF over-expression results in a dramatic rise in cell proliferation, primarily in microglia/macrophages. Astrocytes are not stimulated to proliferate but are activated by the elevated LIF. LIF over-expression also causes the development of severe hindlimb motor dysfunction, an effect mediated by the enhanced activation of microglia/macrophages, as inhibiting microglial activation with minocycline attenuates these motor deficits. Conversely, proliferation is significantly diminished and the microglial/macrophage response to spinal cord injury is much less in the LIF KO compared to wild type (WT). Thus, LIF is a potent pro-inflammatory factor in the adult spinal cord and represents a potential target for the manipulation of inflammatory reactions after spinal cord injury.

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Additional Information:© 2004 Elsevier Inc. Received 22 January 2004; revised 16 March 2004; accepted 8 April 2004. We thank Romulo de Castro for assistance in setting up spinal cord surgery, Jan Ko for assistance in portions of the immunohistochemistry and Doreen McDowell for laboratory administration. The work was supported by funds from the Roman Reed Spinal Cord Injury Research Fund of California, the McGrath Foundation, Nancy Hicks, the Gimble Discovery Fund in Neuroscience and an Elizabeth Ross postdoctoral Fellowship.
Funding AgencyGrant Number
Roman Reed Spinal Cord Injury Research Fund of CaliforniaUNSPECIFIED
McGrath FoundationUNSPECIFIED
Gimble Discovery FundUNSPECIFIED
Elizabeth Ross postdoctoral fellowshipUNSPECIFIED
Subject Keywords:IL-6; Inflammation; gp130; ALS
Issue or Number:2
Record Number:CaltechAUTHORS:20160122-105354941
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Official Citation:Bradley J. Kerr, Paul H. Patterson, Potent pro-inflammatory actions of leukemia inhibitory factor in the spinal cord of the adult mouse, Experimental Neurology, Volume 188, Issue 2, August 2004, Pages 391-407, ISSN 0014-4886, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63890
Deposited By: Ruth Sustaita
Deposited On:22 Jan 2016 22:22
Last Modified:10 Nov 2021 23:22

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