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Akut iskemik inmede serum interlökin-6 düzeylerinin lezyon büyüklüğü ve erken dönem fonksiyonel kötüleşme ile ilişkisi

Year 2018, Volume: 2 Issue: 2, 102 - 110, 02.07.2018
https://doi.org/10.30565/medalanya.386697

Abstract

Amaç: Bu çalışmada, akut dönemde serum İnterlökin-6 (IL-6) düzeylerinin iskemik lezyon büyüklüğü, lokalizasyonu ve hastalığın erken dönem nörolojik fonksiyonel kötüleşmesi ile ilişkisi araştırıldı. 

Hastalar ve Yöntem: Çalışmaya akut serebral infarkt tanısı alan 55 olgu alındı. Kontrol grubu, benzer yaş aralığında 25 sağlıklı gönüllüden oluşturuldu. Olgular BBT’de infarkt yeri ve büyüklüğüne göre dört gruba ayrıldı. Modifiye Rankin Skoru ile erken dönem fonksiyonel kötüleşme değerlendirildi. 

Bulgular: Serum IL-6 seviyeleri sağlıklı kontrol grubuna göre tüm hasta gruplarında anlamlı olarak daha yüksek saptandı (p=0.001). Bilgisayarlı beyin tomografisinde (BBT) büyük lezyonu olanların IL-6 düzeyleri, küçük olanlara göre anlamlı olarak daha yüksek saptandı; ancak lezyon yerleşimi açısından anlamlı farklılık yoktu. Erken dönem fonksiyonel kötüleşmesi daha fazla olan olguların IL-6 değerleri, erken dönem fonksiyonel durumları iyi olan gruba göre anlamlı olarak daha yüksekti. IL-6 düzeyleri ile lökosit sayısı ve fibrinojen düzeyleri arasında anlamlı zayıf korelasyon saptandı. 













Sonuç: Serum IL-6 düzeyi yüksekliğinin lezyon büyüklüğü ve erken dönem fonksiyonel kötüleşme ile ilişkili olması; IL-6’nın intratekal salındığını ve inme patofizyolojisinde önemli rol oynayabileceğini düşündürebilir. Ayrıca akut iskemik inme sonrası inflamatuvar yanıtın IL-6 ile değerlendirilmesi serebral infarkt boyutu ve erken dönem fonksiyonel kötüleşmesi hakkında fikir verebilir. 

References

  • 1. Feigin VL, Forouzan MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, et al. Global and regional burden of stoke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet. 2014;383(9913):245-254. Doi: 10.1016/S0140-6736(13)61953-4.
  • 2. Yılmaz G, Granger DN. Cell adhesion molecules and ischemic stroke. Neurol Res. 2008;30(8):783-93. doi: 10.1179/174313208X341085.
  • 3. Vidale S, Consoli A, Arnaboldi M Consoli D. Postischemic inflammation in acute stroke. J Clin Neurol. 2017;13(1):1-9. doi:10.3988/jcn.2017.13.1.1
  • 4. Kawabori M, Yenari MA. İnflammatory responses in brain ischemia. Curr Med Chem. 2015;22(10).1258-77.
  • 5. Allan SM, Rothwell NJ. Cytokines and acute neuodegeneration. Nat Rev Neurosci. 2001:2(10):734-44.
  • 6. Denes A, Thornton P, Rothwell SM, Allan SM. Inflammation and brain injury: Acute cerebral ischemia, peripheral and central inflammation. Brain Behav Immun. 2010;24(5):708-23.
  • 7. Hirano T. The biology of interleukin-6. ChemImmunol. 1992;51:153-80.
  • 8. Fassbander K, Mössner R, Motsch L. et al. Circulating selecting-and immunoglobulin-typer adhesion molecules in acute ischemic stroke. Stroke. 1995;26(8):1361-4. 9. Kim JS, Yoon SS, Kim YH, Ryu JS. Serial measurement of interleukin-6, transforming growth factor-β, ans S-100 protein in patients with acute stroke. Stroke. 1996;27(9):1553-7.
  • 10. Whiteley W, Wardlaw J, Dennis M, Lowe G, Rumley A, Sattar N, Welsh P, Green A, Andrews M, Sandercock P. Stroke. 2012;43(1):86-91. doi:10.1161/STROKEAHA.111.634089
  • 11. Tarkowski E, Rosengren L, Blomstrand C. et al. Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke. 1995;26(8):1393-8.
  • 12. Schöbitz B, Holsboer F, Kikkert R, Sutanto W, De Kloet ER. Peripheral and central regulation of IL-6 gene expression in endotoxine-treated rats. EndocrRegul. 1992;26(3):103-9.
  • 13. Teasdale G, Maas A, Lecky F, Manley G, Stocchetti N, Murray G. The Glasgow Coma Scale at 40 years: standing the test of time. Lancet Neurol. 2014;13(8):844-54. 
  • 14. Banks JL, Marotta CA. Outcomes validity and reliability of modified rankin scale: implications for stroke cinical trials. Stroke. 2007;38(3):1091-6.
  • 15. Bassuk SS, Rifai N, Ridker PM. High-sensitivity C-reactive protein: clinical importance. CurrProblCardiol. 2004;29(8):439–93.
  • 16. Vila N, Castillo J, Davalos A, Chamorro A. Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke. 2000;31(10):2325-9. 17. Whiteley W, Jackson C, Lewis S, Lowe G, Rumley A, Sandecock P, et al. Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6. Plos Med. 2009;6(9):e1000145. doi: 10.1371/journal.pmed.1000145
  • 18. Bustemante A, Sobrino T, Giralt D, Garcia-Berrocoso T, Llombart V, Ugarriza I, et al. Prognostic value of blood interleukin-6 in the prediction of functional outcome after stroke: a systematic review and meta-analysis. J Neuroimmunol. 2014;274(1-12):215-24.
  • 19. Beamer NB, Coull BM, Clark WM, Hazel JS, Silberg JR. Interleukin-6 and interleukin-1 receptor antagonist in acute stroke. Ann Neurol. 1995;37(3):800-4.
  • 20. Jaferzadeh R, Nazlıel B, İrkeç C, Erberg Ş. Akut iskemik inmede proinflamatuvar sitokinlerin rolü. Türk Nöroloji Dergisi. 2007;13(1):5-11.
  • 21. Emsley HC, Smith CJ, Tyrrell PJ, Hopkins SJ. Inflammation in acute ischemic stroke and its revelance to stroke critcal care. Neurocrit Care. 2008;9(1).125-38.
  • 22. McColl BW, Allan SM, Rothwell NJ. Systemic infection, inflammation and acute ischemic stroke. Neuroscience 2009;158(3):1049-61. doi: 10.1016/j.neuroscience.2008.08.019.
  • 23. Del Rey D, Besedovsky HO. Metabolic and neuroendocrine effects of proinflammatory cytokines. Eur J Clin Invest. 1992;22(Suppl1):10-5.
  • 24. Aydın A, Utku U, Yılmaz A, Erdogan S. İskemik stroklu olgularda hematolojik faktörlerin erken mortalite ve prognoz üzerine etkisi. Türk Beyin Damar Hastalıkları Dergisi 1997;3:93-6.
  • 25. Akira S, Taga T, Kishimoto T. Interleukin-6 in biology and medicine. AdvImmunol. 1993;54:1-78.
  • 26. Guldiken B, Guldiken S, Turgut B, Turgut N, Demir M, Celik Y, et al. The roles of oxidized low-density lipoprotien and interleukin-6 levels in acute atherothrombotic and lacunar ischemic stroke. Angiology. 2008;59(2):224-9.

The relationship between serum interleukin-6 levels with lesion size and early functional worsening in acute ischemic stroke

Year 2018, Volume: 2 Issue: 2, 102 - 110, 02.07.2018
https://doi.org/10.30565/medalanya.386697

Abstract

Aim: In this study, the relationship between ischemic lesion size, localization and early neurological functional impairment of serum Interleukin-6 (IL-6) levels in the acute phase are investigated. 

Patients and Method: Fifty five patients who are diagnosed acute cerebral infarct by history, neurologic examination and computerized brain tomography (CT) were included in the study. The control group consisted of 25 healthy volunteers of similar age range with the patient group.The patients were subdivided into 4 groups according to the size and localization of the infarct on CT. The early neurologic functional stage was evaluated by modified Rankine Score. 

Results: Serum IL-6 levels were found significantly higher in all patients groups compared to healthy control group (p=0.001). IL-6 levels of patients with large lesions in CT were found significantly higher than that of patients with small lesions, but there were no significant difference with regard to localization of the lesion. IL-6 levels of poor early functional worsening group were found significantly higher than good functional group. There was a significant weak correlation between IL-6 levels and leukocyte count and fibrinogen levels. 













Conclusion: The elevation of serum IL-6 levels correlates with lesion size and prognosis suggesting that IL-6 is intrathecally released and may play an important role in stroke pathophysiology. Furthermore, evaluation of the inflammatory response after acute ischemic stroke with IL-6 may provide insight into the size of the cerebral infarction and deterioration with early function worsening. 

References

  • 1. Feigin VL, Forouzan MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, et al. Global and regional burden of stoke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet. 2014;383(9913):245-254. Doi: 10.1016/S0140-6736(13)61953-4.
  • 2. Yılmaz G, Granger DN. Cell adhesion molecules and ischemic stroke. Neurol Res. 2008;30(8):783-93. doi: 10.1179/174313208X341085.
  • 3. Vidale S, Consoli A, Arnaboldi M Consoli D. Postischemic inflammation in acute stroke. J Clin Neurol. 2017;13(1):1-9. doi:10.3988/jcn.2017.13.1.1
  • 4. Kawabori M, Yenari MA. İnflammatory responses in brain ischemia. Curr Med Chem. 2015;22(10).1258-77.
  • 5. Allan SM, Rothwell NJ. Cytokines and acute neuodegeneration. Nat Rev Neurosci. 2001:2(10):734-44.
  • 6. Denes A, Thornton P, Rothwell SM, Allan SM. Inflammation and brain injury: Acute cerebral ischemia, peripheral and central inflammation. Brain Behav Immun. 2010;24(5):708-23.
  • 7. Hirano T. The biology of interleukin-6. ChemImmunol. 1992;51:153-80.
  • 8. Fassbander K, Mössner R, Motsch L. et al. Circulating selecting-and immunoglobulin-typer adhesion molecules in acute ischemic stroke. Stroke. 1995;26(8):1361-4. 9. Kim JS, Yoon SS, Kim YH, Ryu JS. Serial measurement of interleukin-6, transforming growth factor-β, ans S-100 protein in patients with acute stroke. Stroke. 1996;27(9):1553-7.
  • 10. Whiteley W, Wardlaw J, Dennis M, Lowe G, Rumley A, Sattar N, Welsh P, Green A, Andrews M, Sandercock P. Stroke. 2012;43(1):86-91. doi:10.1161/STROKEAHA.111.634089
  • 11. Tarkowski E, Rosengren L, Blomstrand C. et al. Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke. 1995;26(8):1393-8.
  • 12. Schöbitz B, Holsboer F, Kikkert R, Sutanto W, De Kloet ER. Peripheral and central regulation of IL-6 gene expression in endotoxine-treated rats. EndocrRegul. 1992;26(3):103-9.
  • 13. Teasdale G, Maas A, Lecky F, Manley G, Stocchetti N, Murray G. The Glasgow Coma Scale at 40 years: standing the test of time. Lancet Neurol. 2014;13(8):844-54. 
  • 14. Banks JL, Marotta CA. Outcomes validity and reliability of modified rankin scale: implications for stroke cinical trials. Stroke. 2007;38(3):1091-6.
  • 15. Bassuk SS, Rifai N, Ridker PM. High-sensitivity C-reactive protein: clinical importance. CurrProblCardiol. 2004;29(8):439–93.
  • 16. Vila N, Castillo J, Davalos A, Chamorro A. Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke. 2000;31(10):2325-9. 17. Whiteley W, Jackson C, Lewis S, Lowe G, Rumley A, Sandecock P, et al. Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6. Plos Med. 2009;6(9):e1000145. doi: 10.1371/journal.pmed.1000145
  • 18. Bustemante A, Sobrino T, Giralt D, Garcia-Berrocoso T, Llombart V, Ugarriza I, et al. Prognostic value of blood interleukin-6 in the prediction of functional outcome after stroke: a systematic review and meta-analysis. J Neuroimmunol. 2014;274(1-12):215-24.
  • 19. Beamer NB, Coull BM, Clark WM, Hazel JS, Silberg JR. Interleukin-6 and interleukin-1 receptor antagonist in acute stroke. Ann Neurol. 1995;37(3):800-4.
  • 20. Jaferzadeh R, Nazlıel B, İrkeç C, Erberg Ş. Akut iskemik inmede proinflamatuvar sitokinlerin rolü. Türk Nöroloji Dergisi. 2007;13(1):5-11.
  • 21. Emsley HC, Smith CJ, Tyrrell PJ, Hopkins SJ. Inflammation in acute ischemic stroke and its revelance to stroke critcal care. Neurocrit Care. 2008;9(1).125-38.
  • 22. McColl BW, Allan SM, Rothwell NJ. Systemic infection, inflammation and acute ischemic stroke. Neuroscience 2009;158(3):1049-61. doi: 10.1016/j.neuroscience.2008.08.019.
  • 23. Del Rey D, Besedovsky HO. Metabolic and neuroendocrine effects of proinflammatory cytokines. Eur J Clin Invest. 1992;22(Suppl1):10-5.
  • 24. Aydın A, Utku U, Yılmaz A, Erdogan S. İskemik stroklu olgularda hematolojik faktörlerin erken mortalite ve prognoz üzerine etkisi. Türk Beyin Damar Hastalıkları Dergisi 1997;3:93-6.
  • 25. Akira S, Taga T, Kishimoto T. Interleukin-6 in biology and medicine. AdvImmunol. 1993;54:1-78.
  • 26. Guldiken B, Guldiken S, Turgut B, Turgut N, Demir M, Celik Y, et al. The roles of oxidized low-density lipoprotien and interleukin-6 levels in acute atherothrombotic and lacunar ischemic stroke. Angiology. 2008;59(2):224-9.
There are 24 citations in total.

Details

Primary Language Turkish
Subjects ​Internal Diseases
Journal Section Research Article
Authors

Aynur Yılmaz Avcı

Ahmet Muzaffer Demir

Ufuk Utku This is me

Adile Özden Vural This is me

Galip Ekuklu

Publication Date July 2, 2018
Submission Date January 30, 2018
Acceptance Date April 7, 2018
Published in Issue Year 2018 Volume: 2 Issue: 2

Cite

Vancouver Yılmaz Avcı A, Demir AM, Utku U, Vural AÖ, Ekuklu G. Akut iskemik inmede serum interlökin-6 düzeylerinin lezyon büyüklüğü ve erken dönem fonksiyonel kötüleşme ile ilişkisi. Acta Med. Alanya. 2018;2(2):102-10.

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