A patient develops a chronic non-healing wound. Pathological examination shows dense macrophage infiltration, plasma cells, lymphocytes, and angiogenesis with connective tissue deposition. The macrophages show M2 polarisation (CD163+, CD206+). Which cytokine profile is most responsible for the M2 macrophage polarisation seen in chronic wound/fibrotic tissue?

• A IFN-gamma from Th1 cells and NK cells driving M1 polarisation with iNOS and TNF-alpha
• B IL-17A from Th17 cells driving neutrophilic and M1 macrophage recruitment
• C IL-4 and IL-13 from Th2 cells and mast cells driving STAT6-dependent M2 polarisation ✓
• D IL-12 from dendritic cells driving Th1 differentiation and M1 macrophage activation

Explanation

M2 (alternatively activated) macrophage polarisation is primarily driven by Th2 cytokines IL-4 and IL-13, which signal through IL-4Ralpha/gamma common chain and activate STAT6 transcription factor. STAT6 upregulates M2 markers such as CD163, CD206 (mannose receptor), arginase-1 (converting arginine to ornithine/polyamines for tissue repair rather than NO synthesis), and TGF-beta1/IL-10 production. M2 macrophages promote fibrosis, angiogenesis and tissue remodelling. IL-2 and M-CSF also contribute. IFN-gamma drives M1 (classical) activation with pro-inflammatory and antimicrobial functions. IL-17A drives Th17-mediated neutrophilic inflammation.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.