We studied spontaneous and ex vivo activated cytokine production by blood cells of male Wistar rats with different resistance to hypoxia against the background of an LPS-induced systemic inflammatory response. In rats with low (LR) and high resistance (HR) to hypoxia, the number of leukocytes, granulocytes, and peripheral blood lymphocytes was determined, the levels of spontaneous and stimulated production of IL-1β and IL-10 and their ratio were assessed ex vivo. Against the background of a systemic inflammatory response, only HR animals showed a decrease in spontaneous and stimulated production of IL-1β and spontaneous production of IL-10. The IL-1β/IL-10 ratio decreased only in LR rats during the development of a systemic inflammatory response, while in HR animals, no changes in this indicator were observed. The obtained data suggest a high proinflammatory potential of blood cells in LR rats, which apparently determines the development of a more severe course of the systemic inflammatory response.
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References
Chakraborty RK, Burns B. Systemic Inflammatory Response Syndrome. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.
Grégoire M, Tadié JM, Uhel F, Gacouin A, Piau C, Bone N, Le Tulzo Y, Abraham E, Tarte K, Zmijewski JW. Frontline Science: HMGB1 induces neutrophil dysfunction in experimental sepsis and in patients who survive septic shock. J. Leukoc. Biol. 2017;101(6):1281-1287. doi: https://doi.org/10.1189/jlb.5HI0316-128RR
Ono Y, Sakamoto K. Lipopolysaccharide inhibits myogenic differentiation of C2C12 myoblasts through the Toll-like receptor 4-nuclear factor-κB signaling pathway and myoblast-derived tumor necrosis factor-α. PLoS One. 2017;12(7):e0182040. doi: https://doi.org/10.1371/journal.pone.0182040
Biddlestone J, Bandarra D, Rocha S. The role of hypoxia in inflammatory disease (review). Int. J. Mol. Med. 2015;35(4):859-869. doi: https://doi.org/10.3892/ijmm.2015.2079
Dzhalilova DS, Kosyreva AM, Diatroptov ME, Ponomarenko EA, Tsvetkov IS, Zolotova NA, Mkhitarov VA, Khochanskiy DN, Makarova OV. Dependence of the severity of the systemic inflammatory response on resistance to hypoxia in male Wistar rats. J. Inflamm. Res. 2019;12:73-86. doi: https://doi.org/10.2147/JIR.S194581
D’Ignazio L, Shakir D, Batie M, Muller HA, Rocha S. HIF-1β positively regulates NF-κB activity via direct control of TRAF6. Int. J. Mol. Sci. 2020;21(8):3000. doi: https://doi.org/10.3390/ijms21083000
D’Ignazio L, Bandarra D, Rocha S. NF-κB and HIF crosstalk in immune responses. FEBS J. 2016;283(3):413-424. doi: https://doi.org/10.1111/febs.13578
Jain K, Suryakumar G, Ganju L, Singh SB. Differential hypoxic tolerance is mediated by activation of heat shock response and nitric oxide pathway. Cell Stress Chaperones. 2014;19(6):801-812. doi: https://doi.org/10.1007/s12192-014-0504-9
Ghosh D, Kumar R, Pal K. Individual variation in response to simulated hypoxic stress of rats. Indian J. Exp. Biol. 2012;50(10):744-748.
Dzhalilova DS, Diatroptov ME, Tsvetkov IS, Makarova OV, Kuznetsov SL. Expression of Hif-1α, Nf-κb, and Vegf genes in the liver and blood serum levels of HIF-1α, Erythropoietin, VEGF, TGF-β, 8-Isoprostane, and Corticosterone in Wistar rats with high and low resistance to hypoxia. Bull. Exp. Biol. Med. 2018;165(6):781-785. doi: https://doi.org/10.1007/s10517-018-4264-x
Dzhalilova DSh, Kosyreva AM, Diatroptov ME, Makarova MA, Makarova OV. Liver and lung morphology and phagocytic activity of peripheral blood cells during systemic inflammatory response in male rats with different resistance to hypoxia. Klin. Eksper. Morfol. 2019;8(1):47-55. Russian. doi: https://doi.org/10.31088/2226-5988-2019-29-1-47-55
Davletova KI, Mikhaylova ES, Varaksin NA, Zhurakovsky LP, Proskura AV, Sidorov SV, Autenshlyus AI. Cytokines production by blood immune cells in patients of different age groups with invasive ductal carcinoma of no special type and lymphatic metastases. Med. Immunol. 2019;21(6):1115-1126. Russian. doi: https://doi.org/10.15789/1563-0625-2019-6-1115-1126
Bondar SS, Terekhov IV. The production of cytokines and the activity of phagocytic cells in whole blood under conditions of inflammation subclinical and their correction in the experiment. Mezhdunarod. Nauch. Issled. Zh. 2016;(4-5):52-57. Russian. doi: https://doi.org/10.18454/IRJ.2016.46.296
Gergenreter YuS, Zakharova NB, Morozova OL. Tumour microenvironment markers in spontaneous and induced incubation of breast cancer biopsies. Sechenov. Vestn. 2021;12(1):50-59. Russian. doi: https://doi.org/10.47093/2218-7332.2021.12.1.50-59
Sitdikova T, Prosekova E, Zhdanova O. Immunotropic therapy of allergen-induced phenotype of bronchial asthma in children: rationale and clinical and immunological aspects of the performance. Ross. Immunol. Zh. 2018;12(4):743-745. Russian. doi: https://doi.org/10.31857/S102872210002659-9
Kosyreva AM, Makarova OV, Kakturskiy LV, Mikhailova LP, Boltovskaya MN, Rogov KA. Sex differences of inflammation in target organs, induced by intraperitoneal injection of lipopolysaccharide, depend on its dose. J. Inflamm. Res. 2018;11:431-445. doi: https://doi.org/10.2147/JIR.S178288
Zorina VN, Promzeleva NV, Zorin NA, Ryabicheva TG, Zorina RM. Production of proinflammatory cytokines and alpha-2-macroglobulin by peripheral blood cells in the patients with colorectal cancer. Med. Immunol. 2016;18(5):483-488. Russian. doi: https://doi.org/10.15789/1563-0625-2016-5-483-488
Ogryzko NV, Lewis A, Wilson HL, Meijer AH, Renshaw SA, Elks PM. Hif-1α-induced expression of IL-1β protects against mycobacterial infection in Zebrafish. J. Immunol. 2019;202(2):494-502. doi: https://doi.org/10.4049/jimmunol.1801139
Biju MP, Neumann AK, Bensinger SJ, Johnson RS, Turka LA, Haase VH. Vhlh gene deletion induces Hif-1-mediated cell death in thymocytes. Mol. Cell Biol. 2004;24(20):9038-9047. doi: https://doi.org/10.1128/MCB.24.20.9038-9047.2004
Neumann AK, Yang J, Biju MP, Joseph SK, Johnson RS, Haase VH, Freedman BD, Turka LA. Hypoxia inducible factor 1 alpha regulates T cell receptor signal transduction. Proc. Natl Acad. Sci. USA. 2005;102(47):17 071-17 076. doi: https://doi.org/10.1073/pnas.0506070102
Huang Z, Fu Z, Huang W, Huang K. Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: A meta-analysis. Am. J. Emerg. Med. 2020;38(3):641-647. doi: https://doi.org/10.1016/j.ajem.2019.10.023
Drăgoescu AN, Pădureanu V, Stănculescu AD, Chiuțu LC, Tomescu P, Geormăneanu C, Pădureanu R, Iovănescu VF, Ungureanu BS, Pănuș A, Drăgoescu OP. Neutrophil to Lymphocyte Ratio (NLR) — A useful tool for the prognosis of sepsis in the ICU. Biomedicines. 2021;10(1):75. doi: https://doi.org/10.3390/biomedicines10010075
Forget P, Khalifa C, Defour JP, Latinne D, Van Pel MC, De Kock M. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Res. Notes. 2017;10(1):12. doi: https://doi.org/10.1186/s13104-016-2335-5
Faix JD. Biomarkers of sepsis. Crit. Rev. Clin. Lab Sci. 2013;50(1):23-36. doi: https://doi.org/10.3109/10408363.2013.764490
Balk R, Roger C. Bone, MD and the evolving paradigms of sepsis. Contrib. Microbiol. 2011;17:1-11. doi: https://doi.org/10.1159/000323970
Andaluz-Ojeda D, Bobillo F, Iglesias V, Almansa R, Rico L, Gandía F, Resino S, Tamayo E, de Lejarazu RO, Bermejo-Martin JF. A combined score of pro- and anti-inflammatory interleukins improves mortality prediction in severe sepsis. Cytokine. 2012;57(3):332-336. doi: https://doi.org/10.1016/j.cyto.2011.12.002
Taylor CT, Scholz CC. The effect of HIF on metabolism and immunity. Nat. Rev. Nephrol. 2022;18(9):573-587. doi: https://doi.org/10.1038/s41581-022-00587-8
Krzywinska E, Stockmann C. Hypoxia, metabolism and immune cell function. Biomedicines. 2018;6(2):56. doi: https://doi.org/10.3390/biomedicines6020056
Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH, Zheng L, Gardet A, Tong Z, Jany SS, Corr SC, Haneklaus M, Caffrey BE, Pierce K, Walmsley S, Beasley FC, Cummins E, Nizet V, Whyte M, Taylor CT, Lin H, Masters SL, Gottlieb E, Kelly VP, Clish C, Auron PE, Xavier RJ, O’Neill LA. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature. 2013;496:238-242. doi: https://doi.org/10.1038/nature11986
Gleeson LE, Sheedy FJ, Palsson-McDermott EM, Triglia D, O’Leary SM, O’Sullivan MP, O’Neill LA, Keane J. Cutting Edge: Mycobacterium tuberculosis induces aerobic glycolysis in human alveolar macrophages that is required for control of intracellular bacillary replication. J. Immunol. 2016;196(6):2444-2449. doi: https://doi.org/10.4049/jimmunol.1501612
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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 3, pp. 208-214, September, 2023
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Kosyreva, A.M., Dzhalilova, D.S., Tsvetkov, I.S. et al. Ex Vivo Production of IL-1β and IL-10 by Activated Blood Cells of Wistar Rats with Different Resistance to Hypoxia after Systemic Inflammatory Response Syndrome. Bull Exp Biol Med 176, 290–296 (2023). https://doi.org/10.1007/s10517-024-06010-5
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DOI: https://doi.org/10.1007/s10517-024-06010-5