Neuronal Interleukin-4 as a Modulator of Microglial Pathways and Ischemic Brain Damage.

Depending on the activation signal, microglia/macrophages (MΦ) can behave as "healing" (M2) or "harmful" (M1). In response to ischemia, damaged/necrotic brain cells discharge factors that polarize MΦ to a M1-like phenotype. This polarization emerges early after stroke and persists for days to weeks, driving secondary brain injury via proinflammatory mediators and oxidative damage. Our study demonstrates that, to offset this M1-like polarization process, sublethally ischemic neurons may instead secrete a potent M2 polarizing cytokine, interleukin-4 (IL-4). In the presence of IL-4 (including when IL-4 is administered exogenously), MΦ become more effective in the cleanup of ischemic debris and produce trophic factors that may promote brain repair. We propose that IL-4 could represent a potential target for ischemic stroke treatment/recovery.