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

Bei Zhang1, William M Bailey1, Kaitlyn J Braun1

  • 1Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY 40536, United States.

Experimental Neurology
|August 13, 2015
PubMed

Insights

Aging impairs spinal cord injury (SCI) recovery by reducing beneficial M2b macrophages. This age-related shift in immune response exacerbates damage and hinders functional outcomes after SCI.

Area of Science:

  • Neuroscience
  • Immunology
  • Regenerative Medicine

Background:

  • Spinal cord injury (SCI) involves complex immune responses with M1 macrophages promoting injury and M2 macrophages aiding recovery.
  • Increasing average age at SCI necessitates understanding how physiological factors like aging influence macrophage activation.
  • Interleukin-10 (IL-10) is a key marker for M2 macrophage activation, crucial for anti-inflammatory responses.

Purpose of the Study:

  • To investigate the impact of aging on macrophage activation states, specifically IL-10 expression, following SCI.
  • To determine if age influences the abundance of M2b (regulatory) macrophages after SCI.
  • To correlate age-dependent changes in macrophage phenotype with functional recovery and tissue damage post-SCI.

Main Methods:

  • Induction of mild-moderate SCI in young (4-month-old) and aged (14-month-old) mice.
  • Quantification of IL-10 expression and CD86/IL-10 positive (M2b) macrophages in injured spinal cord tissue.
  • Assessment of functional recovery and histological analysis of tissue damage.
  • In vitro studies of M2b macrophage-derived cytokines and neurotoxicity.

Main Results:

  • A significant age-dependent reduction in IL-10 expression was observed in the injured spinal cord of older mice.
  • The population of CD86/IL-10 positive (M2b) macrophages was significantly lower in 14-month-old SCI mice compared to 4-month-old mice.
  • Reduced M2b macrophage presence in aged mice correlated with impaired functional recovery and increased secondary tissue damage.
  • In vitro, M2b macrophages exhibited anti-inflammatory properties without neurotoxicity.

Conclusions:

  • Age is a critical factor modulating the inflammatory response and recovery outcomes after SCI, even following mild to moderate injuries.
  • The age-related decrease in M2b macrophage activation may contribute to heightened secondary injury processes and poorer functional recovery.
  • The M2b macrophage phenotype represents a potential therapeutic target for improving SCI outcomes in aged individuals.