Macrophage Polarisation

Macrophage polarisation is the observation that macrophages adopt distinct functional programmes according to what they encounter. The classical M1 state is produced in culture by lipopolysaccharide with interferon gamma and is marked by inducible nitric oxide synthase, TNF-alpha and IL-12 output and microbial killing. The alternative M2 state is produced by IL-4 or IL-13 and is marked by arginase-1, CD206, IL-10 and TGF-beta, matrix deposition and clearance of apoptotic cells. The nomenclature borrows from the Th1 and Th2 scheme and shares its weakness: it names two ends of a continuum.

In tissue the sequence matters more than the labels. Wound repair runs an early inflammatory phase in which macrophages clear debris and bacteria, then a switch toward a reparative phenotype that supports angiogenesis and matrix deposition. Failure shows at both ends: persistent M1-like activation is a feature of non-healing wounds, sustained M2-like activity drives fibrosis, and tumour-associated macrophages carry an M2-like profile that suppresses antitumour immunity.

This is why a shift toward M2 is not by itself a benefit claim. The useful questions are which phase of which process, in which tissue, and whether the shift persists. Human macrophages in vivo rarely match either archetype, and single-cell work has replaced the two-state picture with overlapping, stimulus-specific programmes.

The error to watch for is a marker panel standing in for function. A study showing that a peptide raises CD206 and lowers inducible nitric oxide synthase in RAW 264.7 cells, a murine leukaemia-derived line, has measured surface protein and transcript changes in a cancer cell line under one artificial stimulus. It has not shown wound healing, resolution of inflammation, or any change in a living animal.