Biological Systems: Theory and Innovation

Theoretical aspects of the formation of key elements of the macrophage activation dichotomy concept: Literature review

Anhelina Andriushchenko
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Abstract

The aim of this study was to analyse the theoretical aspects of the formation of the macrophage activation dichotomy concept (M1/M2), which, despite the complexity of immune response regulation, reflects the existence of a highly efficient multilevel system controlling macrophage functional states and ensuring the proper course of inflammatory processes. Disruption of this system is associated with the development of pathological conditions, including chronic inflammation and tumour progression. The materials of the study consisted of contemporary publications presenting data from fundamental and experimental research on the mechanisms of macrophage activation and polarisation. The methods used include systematisation, comparative analysis, and generalisation of modern scientific approaches, with emphasis on molecular mechanisms and recent technological advances. The classical model of macrophage polarisation distinguishes between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes; however, this classification is increasingly considered oversimplified and does not fully reflect macrophage heterogeneity in vivo. It was shown that cytokines such as interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-β) play a key role in shaping macrophage phenotypes and regulating their involvement in inflammation, tissue repair, and tumour microenvironment processes. Furthermore, macrophages are capable of simultaneously expressing features of different activation programmes, forming mixed or hybrid phenotypes. Based on the analysis of current data, it was concluded that the M1/M2 dichotomy has limited explanatory capacity and should be replaced by a model that considers macrophage activation as a dynamic continuum dependent on microenvironmental conditions. The results of this study may be useful for researchers and clinicians in immunology and oncology for improving approaches to immunomodulatory therapy and the development of targeted treatment strategies

Keywords

macrophage polarisation; M1/M2; cytokines; immune regulation; inflammation; plasticity; tumour microenvironment

Suggested citation
Andriushchenko, A. (2026). Theoretical aspects of the formation of key elements of the macrophage activation dichotomy concept: Literature review. Biological Systems: Theory and Innovation, 17(2), 76-91. https://doi.org/10.31548/biologiya/2.2026.76
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