Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury

Spinal cord injury (SCI) leads to inflammation, orchestrated by microglia and macrophages, contributing to tissue degeneration. IL-4 and IL-13, anti-inflammatory cytokines, can potentially mitigate this damage. This study investigates the effects of IL-13 and IL-4 administration after SCI on microglia and macrophage phenotype and functional outcomes. Mice injected with IL-13 or IL-4 post-SCI showed that while IL-13 induced anti-inflammatory markers, it didn't improve functional recovery like IL-4 did. The two cytokines prompted different gene signatures in microglia and macrophages. IL-4 shifted the metabolism of these cells from glycolysis to oxidative phosphorylation, which is linked to minimizing cytotoxic responses. The findings suggest that the metabolic state of microglia and macrophages after SCI impacts secondary damage. Boosting oxidative phosphorylation could be a new strategy to reduce the harmful effects of these cells after neurotrauma.

• 1
  IL-13 induced the expression of anti-inflammatory markers in microglia and macrophages after SCI but, in contrast to IL-4, it failed to mediate functional recovery.
• 2
  IL-4, in contrast to IL-13, shifted microglia and macrophage metabolism from glycolytic to oxidative phosphorylation.
• 3
  Macrophages stimulated with IL-4 or IL-13 are not deleterious to neurons, but they become cytotoxic when oxidative metabolism is blocked.