Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice

Journal of Neuroinflammation, 2012 · DOI: 10.1186/1742-2094-9-40 · Published: February 27, 2012

Simple Explanation

Spinal cord injury (SCI) triggers inflammation, which can worsen the damage. However, inflammation is also needed for the spinal cord to regenerate. This study looks at blocking a specific inflammatory signal, interleukin-6 (IL-6), to see if it can help the spinal cord heal after an injury in mice. The researchers used an antibody (MR16-1) to temporarily block IL-6 after SCI. They then looked at how this blockade affected the inflammatory response, specifically the activation of different types of macrophages (immune cells) that can either promote or inhibit inflammation. The study found that blocking IL-6 shifted the balance of macrophage activation towards the anti-inflammatory type (M2), reduced the overall inflammatory response, and improved functional recovery in mice after SCI. These findings suggest that controlling IL-6 signaling could be a therapeutic strategy for SCI.

Study Duration

42 days

Participants

211 adult male Jcl:ICR mice

Evidence Level

Not specified

Key Findings

1
MR16-1 treatment increased the area of spared myelin and promoted nerve fiber regeneration after spinal cord injury.
2
Temporal blockade of IL-6 signaling reduced the levels of pro-inflammatory cytokines (IFN-g and TNF-a) and increased the levels of anti-inflammatory cytokines (IL-4 and IL-13) at the lesion site.
3
MR16-1 treatment shifted the predominant macrophage phenotype from pro-inflammatory M1 to anti-inflammatory M2 at the injury site.

Research Summary

This study investigated the effects of temporal IL-6 signaling blockade on macrophage activation and inflammation following spinal cord injury (SCI) in mice. The results showed that MR16-1 treatment promoted spared myelin, nerve fiber regeneration, and locomotor function recovery after SCI. Temporal blockade of IL-6 signaling promoted the formation of alternatively activated macrophages (M2 phenotype) and modified the inflammatory response, which led to SC regeneration and functional recovery.

Practical Implications

Therapeutic Potential

Temporal blockade of IL-6 signaling could be a potential therapeutic strategy for promoting spinal cord regeneration and functional recovery after injury.

Macrophage Polarization

Modulating macrophage polarization towards the M2 phenotype may offer a novel approach to mitigate inflammation and promote tissue repair in SCI.

Clinical Translation

A humanized version of MR16-1 is already available for treating rheumatoid arthritis, suggesting a feasible option for translational research of therapeutic approaches for SCI in humans in the near future.

Study Limitations

1
The study was conducted in mice, and the results may not be directly applicable to humans.
2
The source of the M2 macrophages (resident microglia vs. hematogenous macrophages) could not be definitively determined.
3
It was not determined whether the regeneration was due to the direct action of the alternatively activated macrophages or to other effects of the blockade of IL-6.

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