Features of systemic inflammatory response formation in patients in the acute period of burn disease

To study the effect of thermal trauma on formation of the systemic inflammatory response 15 patients (10 men and 5 women) aged 20 to 74 years with dermal and deep burns in the acute period of burn disease were examined. The fire was a factor in the thermal damage of 5 victims, 9 patients had burns with boiling water, one person received a high-voltage electric trauma with burns by an electric arc flame with an area of 60% of the body surface. Peripheral blood content of NO products, levels of production of pro- and anti-inflammatory cytokines: IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α and functional activity of monocytes in the nitroblue tetrazolium recovery test were determined. As a result of the study, a tendency to increase the content of NO metabolites in the peripheral blood was established. Decompensation of functional activity of monocytes — activators of phagocytosis and cooperative interactions regulation in antigen presentation reactions and formation of functional response of adaptive immunity effector cells is determined. At the same time, an increase in the content of pro- and anti-inflammatory cytokines has been established, which leads to dysregulation of cytokine interactions due to burns. This category of patients develops a systemic inflammatory reaction. Elevated levels of IL-10 indicate the development of immune suppression reactions in patients with burns. Violation the cytokine interactions regulation system leads to significant systemic inflammation and immune paralysis. These uncontrolled systemic immune events can lead to tissue damage and multiple organ failure in patients with burns.

References

1. Williams F.N., Herndon D.N., Jeschke M.G. (2009) The hypermetabolic response to burn injury and interventions to modify this response. Clin. Plast. Surg., 36(4): 583–596. doi: 10.1016/j.cps.2009.05.001.
2. Jeschke M.G., Gauglitz G.G., Kulp G.A. et al. (2011) Long-term persistance of the pathophysiologic response to severe burn injury. PLoS One, 6(7): e21245. doi: 10.1371/journal.pone.0021245.
3. Stanojcic M., Abdullahi A., Rehou S. et al. (2018) Pathophysiological Response to Burn Injury in Adults. Ann. Surg., 267(3): 576–584. doi: 10.1097/SLA.0000000000002097.
4. Auger C., Samadi O., Jeschke M.G. (2017) The biochemical alterations underlying post-burn hypermetabolism. Biochim. Biophys. Acta Mol. Basis Dis., 1863(10 Pt B): 2633–2644. doi: 10.1016/j.bbadis.2017.02.019.
5. Porter C., Tompkins R.G., Finnerty C.C. et al. (2016) The metabolic stress response to burn trauma: current understanding and therapies. Lancet, 388(10052): 1417–1426. doi: 10.1016/S0140-6736(16)31469-6.
6. Jeschke M.G. (2016) Postburn Hypermetabolism: Past, Present, and Future. J. Burn Care Res., 37(2): 86–96. doi: 10.1097/BCR.0000000000000265.
7. Nielson C.B., Duethman N.C., Howard J.M. et al. (2017) Burns: Pathophysiology of Systemic Complications and Current Management. J. Burn Care Res., 38(1): e469–e481. doi: 10.1097/BCR.0000000000000355.
8. Osuka A., Ogura H., Ueyama M. et al. (2014) Immune response to traumatic injury: harmony and discordance of immune system homeostasis. Acute Med. Surg., 1(2): 63–69. doi: 10.1002/ams2.17.
9. Sood R.F., Gibran N.S., Arnoldo B.D. et al.; Inflammation the Host Response to Injury Investigators (2016) Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults. J. Trauma Acute Care Surg., 80(2): 250–257. doi: 10.1097/TA.0000000000000905.
10. Lynnyk O.M., Osadcha O.I., Kozynets G.P. et al. (2021) Features of the immune response to thermal trauma. Fiziol. Zh., 67(6): 32–39. DOI: doi.org/10.15407/fz67.06.032.
11. Ravat F., Payre J., Peslages P. et al. (2011) La brûlure: une pathologie inflammatoire. Pathol.Biol., 59(3): e63–e72. doi: 10.1016/j.patbio.2009.
12. Kovalenko A.O. (2018) Improvement of surgical treatment of patients with dermal burns through the use of wound dressings [dissertation]. 14.01.03 surgery, Kyiv, 186 p.
13. Molehin A.J., Nichols J., Smith F., Nugent K.M. (2021) Phagocytosis: Biology and Methods. Reference Module in Biomedical Sciences.
14. Lapshina L.A., Kravchun P.G., Titova A.Y., Glebova O.V. (2009) The importance of nitrates and nitrites’ content estimation, as markers of endothelial dysfunction in cardiovascular pathology. Ukr. Med. J., 74(6): 49–53.
15. Kozinets G.P., Оsadcha O.I., Lynnyk O.M., Shmatova O.O. (2018) Influencing of endotheliotropic drugs on parameters of the wound process in patients with burns. Mod. Med. Technol., 39(4): 14–18.
16. Spiller F., Oliveira Formiga R., Fernandes da Silva Coimbra J. et al. (2019) Targeting nitric oxide as a key modulator of sepsis, arthritis and pain. Nitric Oxide, 89: 32–40. doi: 10.1016/j.niox.2019.04.011.
17. Guzik T.J., Korbut R., Adamek-Guzik T. (2003) Nitric oxide and superoxide in inflammation and immune regulation. J. Physiol. Pharmacol., 54(4): 469–487. PMID: 14726604.
18. Maurer M., von Stebut E. (2004) Macrophage inflammatory protein-1. Int. J. Biochem. Cell Biol., 36(10): 1882–1886. doi: 10.1016/j.biocel.2003.10.019.
19. Ogita H., Liao J. (2004) Endothelial function and oxidative stress. Endothelium, 11(2): 123–132. doi: 10.1080/10623320490482664.
20. Kozinets G.P., Оsadcha O.I., Kovalenko O.M., Lynnyk O.M. (2019) Wound process influence on formation systemic inflammatory response and early sepsis in patients with burns in acute period of burn disease. Mod. Me. Technol., 41(2): 13–20. doi: DOI 10.34287/MMT.2(41).2019.33.
21. Didion S.P. (2017) Cellular and Oxidative Mechanisms Associated with Interleukin-6 Signaling in the Vasculature. Int. J. Mol. Sci., 18(12): 2563. doi: 10.3390/ijms18122563.
22. Roberts R.A., Smith R.A., Safe S. et al. (2010) Toxicological and pathophysiological roles of reactive oxygen and nitrogen species. Toxicology, 276(2): 85–94. doi: 10.1016/j.tox.2010.07.009.
23. Boraschi D. (2022) What Is IL-1 for? The Functions of Interleukin-1 Across Evolution. Front Immunol., 13: 872155. doi: 10.3389/fimmu.2022.872155.
24. Galley H.F., Webster N.R. (2004) Physiology of the endothelium. Br. J. Anaesth., 93(1): 105–113. doi: 10.1093/bja/aeh163.
25. Nelms K., Keegan A.D., Zamorano J. et al. (1999) The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev. Immunol., 17: 701–738.
26. Skaria T., Burgener J., Bachli E., Schoedon G. (2016) IL-4 Causes Hyperpermeability of Vascular Endothelial Cells through Wnt5A Signaling. PLoS One, 11(5): e0156002. doi: 10.1371/journal.pone.0156002.
27. French B.M., Sendil S., Sepuru K.M. et al. (2018) Interleukin-8 mediates neutrophil-endothelial interactions in pig-to-human xenogeneic models. Xenotransplantation, 25(2): e12385. doi: 10.1111/xen.12385.
28. Kobayashi Y. (2010) The regulatory role of nitric oxide in proinflammatory cytokine expression during the induction and resolution of inflammation. J. Leukoc. Biol., 88(6): 1157–1162. doi: 10.1189/jlb.0310149.
29. Steen E.H., Wang X., Balaji S. et al. (2020) The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis. Adv. Wound Care (New Rochelle), 9(4): 184–198. doi: 10.1089/wound.2019.1032.
30. Jakubzick C.V., Randolph G.J., Henson P.M. (2017) Monocyte differentiation and antigen-presenting functions. Nat. Rev. Immunol., 17(6): 349–362. doi: 10.1038/nri.2017.28.
31. Varzaneh F.N., Keller B., Unger S. et al. (2014) Cytokines in common variable immunodeficiency as signs of immune dysregulation and potential therapeutic targets — a review of the current knowledge. J. Clin. Immunol., 34(5): 524–543. doi: 10.1007/s10875-014-0053-0.
32. Travis M.A., Sheppard D. (2014) TGF-β activation and function in immunity. Annu Rev. Immunol., 32: 51–82. doi: 10.1146/annurev-immunol-032713-120257.
33. Hur J., Yang H.T., Chun W. et al. (2015) Inflammatory cytokines and their prognostic ability in cases of major burn injury. Ann. Lab. Med., 35(1): 105–110. doi: 10.3343/alm.2015.35.1.105.
34. Dhingra S., Sharma A.K., Arora R.C. et al. (2009) IL-10 attenuates TNF-alpha-induced NF kappaB pathway activation and cardiomyocyte apoptosis. Cardiovasc. Res., 82(1): 59–66. doi: 10.1093/cvr/cvp040.