IL-Mediated Macrophage Polarization Axis: From Inflammatory Positive Feedback Loop to Precision Biomarkers and...

This narrative review comprehensively elaborates the complicated interleukin (IL)-macrophage polarization axis as the core pathogenesis of allergic rhinitis (AR), focusing on layered molecular regulatory mechanisms covering inflammatory signaling, metabolic reprogramming and epigenetic modulation. Pro-inflammatory IL-1β, IL-6, IL-17 and TNF-α bind to TLR receptors to activate NF-κB, NLRP3 inflammasome and PI3K/Akt cascades, triggering M1 macrophage overactivation and acute nasal congestion, rhinorrhea via robust inflammatory mediator release. By contrast, anti-inflammatory IL-4 and IL-10 predominantly activate STAT6 signaling to drive abnormal M2 macrophage accumulation, sustaining persistent type 2 inflammation and irreversible nasal tissue remodeling; notably, IL-17 presents concentration-dependent bidirectional regulation on macrophage phenotypes. Metabolic reprogramming featured with glycolysis-oxidative phosphorylation switch, together with DNA methylation, histone modification and non-cRNA-mediated epigenetic regulation, serve as vital downstream executors linking IL signals to macrophage polarization imbalance. Conventional glucocorticoids, antihistamines and monoclonal antibodies including omalizumab and dupilumab (targeting IL-4Rα) exert therapeutic efficacy via intervening this axis, while multiple natural herbal constituents and classic TCM formulas also modulate relevant inflammatory pathways to alleviate AR symptoms. For translational application, the CD206/CD86 macrophage polarization ratio is highlighted as a representative candidate biomarker for disease severity assessment. Collectively, this review integrates multi-layered regulatory evidence and lays theoretical support for developing novel precision-targeted anti-allergic therapies.