MODERN TREATMENT METHODS OF THE LOCALIZED INFLAMMATORY RESPONSE IN ACUTE CEREBRAL ISCHEMIA

  • V. S. Lychko Sumy State University
Keywords: immune monitoring, cytokine, inflammation, ischemia, interleukine, imbalance

Abstract

The article shows the results of a complex study of the leading index changes of the cytokine profile in patients with the brain infarction (BI) in the course of therapy with human cryopreserved cord blood serum (CCBS). Plasma levels of proinflammatory cytokines (interleukine-6 (IL-6), tumor necrosis factor-α (TNF-α)) as well as anti-inflammatory factors – IL-4, IL‑10 were tested in the blood serum of 350 patients in the mentioned medical condition on the 1st, 10th and 21st days of therapy.

All patients were divided into 2 groups: the 1st one (n = 175) got undifferentiated therapy with the additional administration of acetylsalicylic acid (ASA); the 2nd one (n = 175) got the therapy of 1st group complemented by administration of 1 ml of CCBS within 10 days. Additionally there were 2 more clinical sub-groups distinguished by National Institutes of Health Stroke Scale (NIHSS) according to disease severity level: A group (n = 183) included patients in medium severity condition; B group (n = 167) comprised patients in critical condition. Plasma levels of IL-4, IL-6, IL-10 and TNF-α were specified by means of enzyme-linked immunosorbent analysis.

Summing up the above-mentioned, it is certain that the imbalance in immune system functioning, represented by a simultaneous lytic level increase of both proinflammatory (IL-6, TNF-α) and anti-inflammatory (IL‑4, IL-10) cytokines, is observed shortly after the start of BI.

Additional administration of CCBS in a therapeutic complex caused more considerable and more rapid stabilization of proinflammatory factor values, which were ultimately close to the control ones. This substantially influenced the course of disease and its prognosis. The research showed no accurate reduction in anti-inflammatory cytokines levels of ІL-4 and ІL-10 which indicated intensive localized inflammatory response even at the end of the acute period of disease. However, comparing the mentioned values with those of the patients who were not additionally treated with CCBS, lower value levels have to be acknowledged. It may be explained by a more efficient and incipient reduction of proinflammatory cytokines concentration in the course of disease, which in its turn results in normalization of ІL-4 and ІL-10 levels.

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References

Boehme AK, McClure LA, Zhang Y et al. [Inflammatory markers and outcomes after lacunar stroke levels of inflammatory markers in treatment of stroke study]. Stroke. 2016; 47 (3): 659–667. doi: 10.1161/strokeaha.115.012166.

Ludewig P, Winneberger J, Magnus T. [The cerebral endothelial cell as a key regulator of inflammatory processes in sterile inflammation]. Journal of Neuroimmunology. 2019; 326: 38–44. doi: 10.1016/j.jneuroim.2018.10.012.

Taga T, Kishimoto T. [gp130 and the interleukin-6 family of cytokines]. Annual Review of Immunology. 1997; 15: 797–819. doi: 10.1146/annurev.immunol.15.1.797.

Erta M, Quintana A, Hidalgo J. [Interleukin-6, a major cytokine in the central nervous system]. International Journal of Biological Sciences. 2012; 8(9): 1254–1266. doi: 10.7150/ijbs.4679.

Whiteley W, Jackson C, Lewis S et al. [Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6]. Plos Medicine. 2009; 6(9). e1000145. doi: 10.1371/journal.pmed.1000145.

Chen AQ, Fang Z, Chen XL et al. [Microglia-derived TNF-alpha mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke]. Cell Death & Disease. 2019; 10: 1–18. doi: 10.1038/s41419-019-1716-9.

Aggarwal BB. [Signalling pathways of the TNF superfamily: A double-edged sword]. Nature Reviews Immunology. 2003; 3(9): 745–756. doi: 10.1038/nri1184.

Gelinas L, Falkenham A, Oxner A et al. [Highly purified human peripheral blood monocytes produce IL-6 but not TNF alpha in response to angiotensin II]. Journal of the Renin-Angiotensin-Aldosterone System. 2011; 12(3): 295–303. doi: 10.1177/1470320310391332.

Leonoudakis D, Zhao P, Beattie EC. [Rapid tumor necrosis factor alpha-induced exocytosis of glutamate receptor 2-lacking AMPA receptors to extrasynaptic plasma membrane potentiates excitotoxicity]. Journal of Neuroscience. 2008; 28(9): 2119–2130. doi: 10.1523/jneurosci.5159-07.2008.

Rath PC, Aggarwal BB. [TNF-induced signaling in apoptosis]. Journal of Clinical Immunology. 1999; 19(6): 350–364. doi: 10.1023/a:1020546615229.

Montgomery SL, Bowers WJ. [Tumor necrosis factor-alpha and the roles it plays in homeostatic and degenerative processes within the central nervous system]. Journal of Neuroimmune Pharmacology. 2012; 7(1): 42–59. doi: 10.1007/s11481-011-9287-2.

Zhang HR, Park YJ, Wu JX et al. [Role of TNF-alpha in vascular dysfunction]. Clinical Science. 2009; 116(3-4): 219–230. doi: 10.1042/cs20080196.

Zou JY, Crews FT. [TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition]. Brain Research. 2005; 1034(1-2): 11–24. doi: 10.1016/j.brainres.2004.11.014.

Zhao WH, Xie WJ, Xiao Q et al. [Protective effects of an anti-inflammatory cytokine, interleukin-4, on motoneuron toxicity induced by activated microglia]. Journal of Neurochemistry. 2006; 99(4): 1176–1187. doi: 10.1111/j.1471-4159.2006.04172.x.

Lee YW, Kuhn H, Hennig B et al. [IL-4-induced oxidative stress upregulates VCAM-1 gene expression in human endothelial cells]. Journal of Molecular and Cellular Cardiology. 2001; 33(1): 83–94. doi: 10.1006/jmcc.2000.1278.

Lewis DB, Yu CC, Meyer J et al. [cellular and molecular mechanisms for reduced interleukin-4 and interferon-gamma production by neonatal T-cells]. Journal of Clinical Investigation. 1991; 87(1): 194–202. doi: 10.1172/jci114970.

Garg SK, Kipnis J, Banerjee R. [IFN-gamma and IL-4 differentially shape metabolic responses and neuroprotective phenotype of astrocytes]. Journal of Neurochemistry. 2009; 108(5): 1155–1166. doi: 10.1111/j.1471-4159.2009.05872.x.

Paul WE. [Interleukin-4 – a prototypic immunoregulatory lymphokine]. Blood. 1991; 77(9): 1859–1870.

Garcia JM, Stillings SA, Leclerc JL et al. [Role of interleukin-10 in acute brain injuries]. Frontiers in Neurology. 2017; 8:244. doi: 10.3389/fneur.2017.00244.

Kang H, Yang PY, Rui YC. [Adenovirus viral interleukin-10 inhibits adhesion molecule expressions induced by hypoxia/reoxygenation in cerebrovascular endothelial cells]. Acta Pharmacol Sin. 2008; 29(1): 50–56. doi: 10.1111/j.1745-7254.2008.00718.x.

Liesz A, Suri-Payer E, Veltkamp C et al. [Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke]. Nature Medicine. 2009; 15(2): 192–199. doi: 10.1038/nm.1927.

Kinzenbaw DA, Chu Y, Pena Silva RA et al. [Interleukin-10 protects against aging-induced endothelial dysfunction]. Physiol Rep. 2013; 1(6): e00149. doi: 10.1002/phy2.149.

Dace DS, Khan AA, Kelly J et al. [Interleukin-10 promotes pathological angiogenesis by regulating macrophage response to hypoxia during development]. Plos One. 2008; 3(10). doi: 10.1371/journal.pone.0003381.

Wang Q, Tang XN, Yenari MA. [The inflammatory response in stroke]. Journal of Neuroimmunology. 2007; 184(1-2): 53–68. doi: 10.1016/j.jneuroim.2006.11.014.

Hu XM, Li PY, Guo YL et al. [Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia]. Stroke. 2012; 43(11): 3063–3074. doi: 10.1161/strokeaha.112.659656.

Published
2020-03-29
How to Cite
1.
V. S. Lychko. MODERN TREATMENT METHODS OF THE LOCALIZED INFLAMMATORY RESPONSE IN ACUTE CEREBRAL ISCHEMIA. East Ukr Med J [Internet]. 2020Mar.29 [cited 2024Mar.29];8(1):8-14. Available from: https://eumj.med.sumdu.edu.ua/index.php/journal/article/view/66