Molecular Balancing Act

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Macrophages and microglia are two types of highly specialized cells. Both play a key role in maintaining the nervous system healthy and balanced. However, in case of an injury, they can adopt several forms, which may lead to opposite effects on tissue repair.

After spinal cord injury, microglia and macrophages transform into the so-called M1 or M2 type. The M1 type typically activates inflammation and contributes to further tissue damage. The M2 type on the other hand is capable of diminishing inflammation and promotes tissue repair. Unfortunately, most macrophages and microglia turn into the unwanted M1 type.

Doctor Rubèn López-Vales, from the Universitat Autònoma de Barcelona in Spain, recently published an article in the journal Glia that might open a doorway to manipulate this mechanism in a positive way. He found out that a molecule named Interleukin 4 is able to control the switch from the unwanted M1 to the needed M2 type. Interleukin 4 belongs to the family of Cytokines; small proteins released throughout the body to control inflammatory and immune responses. 

Within an experiment, Doctor López-Vales injected Interleukin 4 into the spinal cord two days after injury. In doing so, he was able to increase the expression of M2 markers in both microglia and macrophages. Further analysis showed that Interleukin 4 could enhance resolution of inflammation, an event that is classically associated with damage decrease and recovery of healthy tissue. The team was then able to confirm that the Interleukin 4 treatment improved functional outcomes and reduced tissue damage after injury.

So, what will happen next?
The scientists are not hundred per cent sure if these improvements result by the presence of macrophages with M2 markers so further analysis will have to determine this. Although still at a preliminary stage, this analysis suggest that therapies aiming at increasing Interleukin 4 levels could be valuable for the treatment of acute spinal cord injuries.
Doctor Rubèn López-Vales received a grant from Wings for Life in the past, and the foundation is proud to see that funded scientists are actively contributing to the field.

Source: Francos-Quijorna I, Amo-Aparicio J, Martinez-Muriana A, López-Vales R. IL-4 drives microglia and macrophages toward a phenotype conducive for tissue repair and functional recovery after spinal cord injury. Glia. 2016 Jul 29.