M1/M2 macrophage polarization

The M1/M2 framework describes macrophage activation states at two functional extremes: M1 (classically activated) macrophages, induced by IFN-γ and LPS, produce pro-inflammatory mediators including TNF-α, IL-6, IL-12, and reactive oxygen species; M2 (alternatively activated) macrophages, induced principally by IL-4 and IL-13 (and deactivated/suppressed by IL-10), promote tissue repair, phagocytosis of debris, and anti-inflammatory resolution. It is important to note that this binary model is a pedagogical simplification — current transcriptomic and proteomic data support a continuum of macrophage states that do not neatly map onto two poles. With aging, tissue macrophages tend toward a dysregulated inflammatory baseline, impairing resolution of acute inflammation and contributing to the chronic sterile inflammation underlying inflammaging.

Last reviewed: May 7, 2026