Characteristics of local inflammatory reaction formation in patients with chronic wounds

Materials and methods. The study focused on neutrophilic granulocytes, monocytes, reactive oxygen species (ROS), the antioxidant system, and the levels of pro- and anti-inflammatory cytokines in the capillary blood of the wound area. The study involved 20 patients with chronic wounds undergoing treatment at the Burn Unit of Kyiv City Clinical Hospital № 2.

Methods included a clinical prospective analysis, the nitroblue tetrazolium test, measurement of myeloperoxidase activity, ROS and superoxide dismutase levels, as well as enzyme-linked immunosorbent assay to assess the cytokine profile.

Results. Dysfunction in the functional activity of neutrophilic granulocytes in the wound area was identified, including decreased myeloperoxidase activity and an increased number of cells with apoptotic changes. Elevated ROS levels and reduced antioxidant activity of superoxide dismutase were found to contribute to oxidative stress. A significant imbalance between pro-inflammatory cytokines (interleukin-1, tumor necrosis factor-α) and the anti-inflammatory cytokine (interleukin-6) was observed, exacerbating chronic inflammation and hindering wound healing.

Conclusion. Patients with chronic wounds exhibit significant dysfunction of innate immune cells, oxidative stress, and cytokine imbalance, which impede reparative processes and represent critical therapeutic targets.

References

1. Boyko T.V., Longaker M.T., Yang G.P. (2018) Review of the Current Management of Pressure Ulcers. Adv. Wound Care (New Rochelle), 7(2): 57–67.
2. ACS/ASE Core Curriculum for Medical Students: Non-Healing Wounds. http://www.facs.org/-/media/files/education/core-curriculum/nonhealing_wounds.ashx.
3. Snyder D., Sullivan N., Margolis D. et al. (2020) Skin replacement for the treatment of chronic wounds. Rockville (MD) — Agency for Healthcare Research and Quality.
4. Frykberg R.G., Banks J. (2015) Problems in the treatment of chronic wounds. Recommended Wound Care, 4(9): 560–582. DOI: 10.1089/wound.2015.0635.
5. Kavalukas S.L., Barbul A. (2011) Nutrition and wound healing: an update. Plast Reconstruct Surg., 127(Suppl 1): 38S–43S. DOI: 10.1097/PRS.0b013e318201256c.
6. Keller U. (2019) Nutritional laboratory markers for malnutrition. J. Clean Med., 8(6): 775–786. DOI: 10.3390/jcm8060775.
7. Razieva K., Kim Y., Zharkinbekov Z. et al. (2021) Immunology of healing of acute and chronic wounds. Biomolecules, 11: 700. DOI: 10.3390/biom11050700.
8. Wang J. (2018) Neutrophils in tissue injury and repair. Cell. Tis. Res., 371(3): 531–539.
9. Olsson M., Jarbrink K., Diwakar U. et al. (2019) Humanistic and economic time of chronic wounds: a systematic review. Wound Regeneration, 27: 114–125.
10. Cañedo-Dorantes L., Cañedo-Ayala M. (2019) Healing of acute skin wounds: a comprehensive review. Int. J. Inflammation, 2019: 3706315. DOI: 10.1155/2019/3706315.
11. Ellis S., Lin E.J., Tartar D. (2018) Immunology of wound healing. Well. Dermatol. Republic, 7: 350–358. DOI: 10.1159/0000000358.
12. Han G., Havnaer A., Lee H.H. et al. (2020) Biological depletion of neutrophils attenuates inciting markers and the development of the psoriatic phenotype in mouse models of psoriasis. Wedge. Immunol., 210: 108294.
13. Wielgus T.A., Roy S., McDaniel J.C. (2013) Neutrophils and wound healing: positive actions and negative states. Adv. Wound Care, 2: 379–388.
14. Dunnill K., Patton T., Brennan J. et al. (2017) Reactive species of respiration (ROS) and wound healing: the functional role of ROS and new technologies for modulating ROS to enhance the healing process. Int. Rana J., 14: 89–96.
15. Kono K., Koya-Miyata S., Harashima A. et al. (2021) Inflammatory M1-like macrophages polarized by NK-4 induce an enhanced phenotypic switch to an anti-inflammatory M2-like phenotype when cocultured with apoptotic cells. J. Infl., 18(1): 2.
16. Xu Z., Liang B., Tian J., Wu J. (2021) Anti-inflammatory biomaterials for chronic wound healing. Biomater. Sci., 9: 4388–4409. DOI: 10.1039/d1bm00632a.
17. Пастер Є.У. (1989) Імунологія: практикум. Вища школа, Київ, 304 с.
18. Ковальчук Л.В. (2010) Імунологія: практикум. ГЕОТАР-Медіа, Москва, 176 с.
19. Selyutina S.N., Selyutin A.Yu., Pal A.I. (2000) Modification of the determination of the concentration of TBA-active products of blood serum. Wedge. Lab. Diagnostics, 2: 8–11.
20. Костюк В.А., Потапович А.І., Ковальова Ж.В. (1990) Простий та чутливий метод визначення активності супероксиддисмутази, заснований на реакції окислення кверцетину. Зап. мед. хім., 36(2): 88–91.
21. Kelman L., Pivovarova-Ramich O., Pfeiffer A.F.H. et al. (2019) Cytokines for assessing chronic inflammatory status in aging studies: reliability and phenotypic characterization. Immune Aging, 16: 11. DOI: 10.1186/s12979-019-0157-6.