Age decreases macrophage IL-10 expression: Implications for functional recovery and tissue repair in spinal cord injury

Bei Zhang, William M. Bailey, Kaitlyn J. Braun, John C. Gensel

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Macrophages with different activation states are present after spinal cord injury (SCI). M1 macrophages purportedly promote secondary injury processes while M2 cells support axon growth. The average age at the time of SCI has increased in recent decades, however, little is known about how different physiological factors contribute to macrophage activation states after SCI. Here we investigate the effect of age on IL-10, a key indicator of M2 macrophage activation. Following mild-moderate SCI in 4 and 14. month old (MO) mice we detected significantly reduced IL-10 expression with age in the injured spinal cord. Specifically, CD86/IL-10 positive macrophages, also known as M2b or regulatory macrophages, were reduced in 14 vs. 4 MO SCI animals. This age-dependent shift in macrophage phenotype was associated with impaired functional recovery and enhanced tissue damage in 14-month-old SCI mice. In vitro, M2b macrophages release anti-inflammatory cytokines without causing neurotoxicity, suggesting that imbalances in the M2b response in 14-month-old mice may be contributing to secondary injury processes. Our data indicate that age is an important factor that regulates SCI inflammation and recovery even to mild-moderate injury. Further, alterations in macrophage activation states may contribute to recovery and we have identified the M2b phenotype as a potential target for therapeutic intervention.

Original languageEnglish
Pages (from-to)83-91
Number of pages9
JournalExperimental Neurology
Volume273
DOIs
StatePublished - Nov 1 2015

Bibliographical note

Funding Information:
We would like to thank Peter Rock, John Godbout, Ashley Fenn, Phillip Popovich, Amy Tovar, Linda Simmerman, Michael Orr, and Chris Richards for technical advice and support. The current project was made possible by support from a Cardinal Hill Endowment to Joe Springer, the Craig H. Neilsen Foundation , and the NINDS NS051220 P30 grant to the University of Kentucky.

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

  • Adult
  • Aged
  • Aging
  • BMS
  • Brain
  • Contusion
  • Digigait
  • Grid walk
  • IL-12
  • Inflammation
  • Locomotor
  • Macrophage polarity
  • Macrophage polarization
  • Microglia
  • Monocyte: IL-12p40
  • Neuroprotection
  • Neurotrauma
  • Traumatic

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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