Age decreases macrophage IL-10 expression: Implications for functional recovery and tissue repair in spinal cord injury.
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.
Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY 40536, United States.
Bei
B
Zhang
Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY 40536, United States.
William M
WM
Bailey
Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY 40536, United States.
Kaitlyn J
KJ
Braun
Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY 40536, United States. Electronic address: gensel.1@uky.edu.
John C
JC
Gensel
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009068:Movement / Q000502:physiology; D012333:RNA, Messenger; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors
D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D016753:Interleukin-10
Adult; Aged; Aging; BMS; Brain; Contusion; Digigait; Grid walk; IL-12; Inflammation; Locomotor; Macrophage polarity; Macrophage polarization; Microglia; Monocyte: IL-12p40; Neuroprotection; Neurotrauma; Traumatic