Contemporary Strategies for Modulating Immune Response by Regulating the M1/M2 Macrophage Phenotype Balance through Cytokines and Growth Factors

Authors

  • Natalia V. Kolesnikova Kuban State Medical University, Krasnodar, Russia
  • Gleb P. Chuprynin Kuban State Medical University, Krasnodar, Russia
  • Karina I. Melkonian Kuban State Medical University, Krasnodar, Russia

DOI:

https://doi.org/10.17072/1994-9952-2026-2-213-224

Keywords:

Cytokines, immunomodulation, immune cells, macrophage activation

Abstract

Skin wound healing is a cascade of complex biological processes that ensure tissue repair, one of the key mechanisms being macrophage polarization, which regulates the transition from a pro‑inflammatory to an anti‑inflammatory state. Disruptions in this process lead to chronic inflammation, fibrosis, and delayed tissue recovery. Current research aimed at modifying the wound bed microenvironment through immunomodulation focuses on the use of cytokines and growth factors such as IL‑4, IL‑10, PDGF, VEGF, IGF‑1, FGF‑10, and others to modulate macrophage activity. All these biomolecules, when incorporated into nanomaterials and delivery systems, help accelerate healing, reduce scarring, and regulate inflammation. In oncology and inflammatory diseases, the possibility of switching macrophages between M1 and M2 phenotypes is also being studied to achieve therapeutic goals. The effectiveness of such approaches is enhanced by the use of modern carriers that ensure targeted delivery and controlled release of cytokines. This work reviews recent advances in the application of cytokines and growth factors incorporated into various systems to modulate macrophages and their phenotypes, as well as their use in developing personalized and effective treatments for various pathologies, particularly skin injuries.

Author Biographies

  • Natalia V. Kolesnikova, Kuban State Medical University, Krasnodar, Russia
    Doctor of Biological Sciences, Professor, Professor at the Department of Clinical Immunology, Allergology and Laboratory Diagnostics
  • Gleb P. Chuprynin, Kuban State Medical University, Krasnodar, Russia
    PhD student Department of Clinical Immunology, Allergology and Laboratory Diagnostics, Junior Researcher at the Scientific and Technological Center for Biomedicine
  • Karina I. Melkonian, Kuban State Medical University, Krasnodar, Russia
    Candidate of Medical Sciences, Associate Professor, Head of the Central Research Laboratory

References

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38. Scopelliti F. et al. Platelet lysate converts M (IFNγ+ LPS) macrophages in CD206+ TGF‐β+ ar-ginase+ M2‐like macrophages that affect fibroblast activity and T lymphocyte migration. Journal of Tissue Engineering and Regenerative Medicine. V. 15, No 9 (2021): pp. 788-797. DOI: 10.1002/term.3229.

39. Shahbazi M.A. et al. Targeted reinforcement of macrophage reprogramming toward M2 polarization by IL-4-loaded hyaluronic acid particles. ACS Omega. V. 3, No. 12 (2018): pp. 18444-18455. DOI: 10.1021/acsomega.8b03182.

40. Sharifiaghdam M. et al. Macrophages as a therapeutic target to promote diabetic wound healing. Molecular Therapy. V. 30, No. 9 (2022): pp. 2891-2908. DOI: 10.1016/j.ymthe.2022.07.016.

41. Shen D., Chen J. Cardiac macrophages promote polarization of macrophages toward M2 phenotype to improve myocardial remodeling via NGAL after myocardial infarction. Cell Biochemistry and Biophys-ics. V. 83 (2025): pp. 3427-3436. DOI: 10.1007/s12013-025-01726-1.

42. Silveira M.J. et al. Immunostimulatory effects of IL-12 targeted pH-responsive nanoparticles in macrophage-enriched 3D immuno-spheroids in vitro model. Drug Delivery and Translational Research. V. 15 (2025): pp. 4775-4794. DOI: 10.1007/s13346-025-01896-8.

43. Singer M. et al. Modulation of tumor-associated macrophages to overcome immune suppression in the hepatocellular carcinoma microenvironment. Cancers. V. 17, No. 1 (2024). Art. 66. DOI: 10.3390/cancers17010066.

44. Tian G. et al. Cell-free decellularized cartilage extracellular matrix scaffolds combined with inter-leukin 4 promote osteochondral repair through immunomodulatory macrophages: in vitro and in vivo pre-clinical study. Acta biomaterialia. V. 127 (2021): pp. 131-145. DOI: 10.1016/j.actbio.2021.03.054.

45. Torregrossa M. et al. Modulation of macrophage functions by ECM-inspired wound dressings–a promising therapeutic approach for chronic wounds. Biological chemistry. V. 402, No. 11 (2021): pp. 1289-1307. DOI: 10.1515/hsz-2021-0145.

46. Tottoli E.M. Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics. V. 12. No. 8 (2020). Art. 735. DOI: 10.3390/pharmaceutics12080735.

47. Walvekar K.P. et al. Stable expression of human arginase 1 does not suppress inflammation or M1 macrophage polarization in THP-1 monocytes. Next Research. V. 2, No. 3 (2025). Art. 100656. DOI: 10.1016/j.nexres.2025.100656.

48. Xiaoye Z.H.U. et al. Role of M1/M2 macrophages in pain modulation. Journal of Central South University Medical Sciences. V. 49, No. 7 (2024). Art. 1155. DOI: 10.11817/j.issn.16727347.2024.240017.

49. Xin Y. et al. Emu-miR-10a-5p in Echinococcus multilocularis-derived-extracellular vesicles allevi-ates airway inflammation in mice with allergic asthma by inhibiting macrophage M2a polarization through LIF-mediated JAK1–STAT3 signaling. Frontiers in Immunology. V. 16 (2025). Art. 1577349. DOI: 10.3389/fimmu.2025.1577349.

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Published

2026-07-07

How to Cite

Contemporary Strategies for Modulating Immune Response by Regulating the M1/M2 Macrophage Phenotype Balance through Cytokines and Growth Factors. (2026). Bulletin of Perm University. Biology, 17(2), 213-224. https://doi.org/10.17072/1994-9952-2026-2-213-224

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