NEVİN İLHAN, SOLMAZ SUSAM, Ömer CANPOLAT

İskemik/Hemorajik İnmede Serum TNF-α, IL-1β ve TGF-β2 Düzeylerinin ve Oksidan-Antioksidan Durumun Değerlendirilmesi

Amaç: İnme olarak tanımlanan serebrovasküler hastalıklar; ciddi mortalite ve morbiditeye yol açan hastalıklardan biridir. İnme sonrasında proinflamatuvar ve anti-inflamatuvar sitokinlerin üretimi ve sekresyonu hem insan hem de deneysel hayvan modellerinde gösterilmiştir. Bu çalışmanın amacı iskemik ve hemorajik inme patogenezinde serum TNF-α, IL-1β ve TGF-β2 düzeyleri ile oksidatif stres parametrelerinin durumunu değerlendirmektir. Gereç ve Yöntem: Çalışma inme tanısı almış 35 iskemik ve 35 hemorajik inmeli toplam 70 olgu, yaş ve cins olarak benzer 18 sağlıklı bireyde gerçekleştirildi. Oksidan-antioksidan durumunun değerlendirilmesi için total antioksidan durum (TAS) ve toplam oksidan durum (TOS) düzeyleri otoanalizör kullanılarak ölçüldü. Serum TNF-α, IL-1β ve TGF-β2 düzeyleri ELISA yöntemi ile belirlendi. Oksidan-antioksidan durum değerlendirilmesi otoanalizör kullanılarak, total antioksidan durum (TAS) ve toplam oksidan durum (TOS) düzeylerinin ölçülmesiyle gerçekleştirildi. Bulgular: Sağlıklı kontrol deneklerinde serum TNF-α, IL-1β ve TGF-β2 düzeyleri iskemik ve hemorajik inmeli hastalardan anlamlı olarak daha düşüktü. Kontrollere göre her iki hasta grubunda azalmış TAS düzeyleri tespit edildi. Hastalardaki TOS düzeyleri ise, kontrollere göre yaklaşık 8 kat yüksekti. Sonuç: Sonuç olarak, hastalar grupları ve kontroller arasında TNF-α, IL-1β ve TGF-β2 düzeylerinin oldukça farklı olduğu ve bu sitokinlerin inme patolojisinde önemli rol oynayabilecekleri düşünülmektedir. Ayrıca, çalışmadan elde edilen sonuçlar, oksidatif stresin serebrovasküler hastalık gelişimine katkıda bulunabileceğini düşündürmektedir. Konunun tam olarak netlik kazanabilmesi için daha fazla vakanın katıldığı uzun dönem izlem çalışmalarına ihtiyaç vardır.

The Evaluation of Serum TNF-α, IL-1β and TGF-β2 Levels and Oxidant-Antioxidant Status in Ischemic/Hemorrhagic Stroke

Objective: Cerebrovascular diseases, defined as stroke; are one of the diseases that cause serious mortality and morbidity. The secretion and production of proinflammatory and anti-inflammatory cytokines after stroke has been seen in both human and experimental animal models. The aim of this study was to evaluate the serum TNF-α, IL-1β and TGF-β2 levels and the status of oxidative stress parameters in the pathogenesis of ischemic and hemorrhagic stroke. Material and Method: Totally 70 patients, 35 with ischemic stroke and 35 with hemorrhagic stroke, and 18 healthy individuals similar in age and gender with the patients were enrolled in the study. Serum TNF-α, IL-1β and TGF-β levels were determined using ELISA. Total antioxidant status (TAS) and total oxidant status (TOS) levels were measured using autoanalyzer for detecting oxidant-antioxidant state. Results: Serum levels of TNF-α, IL-1β and TGF-β2 were significantly lower in healthy control subjects, than those in patients with ischemic and hemorrhagic stroke. TAS levels were lower in both patient groups compared to controls. TOS levels were almost 8 times higher in patients according to controls. Conclusion: It was suggested that TNF-α, IL-1β and TGF-β2 levels differed highly significantly between stroke patients and controls and these cytokines they may play important role in the stroke pathological process. Moreover, the results obtained from the study suggested that the oxidative stress may contribute to development of cerebrovascular disease. Long term follows up studies with more patients participation are needed to confirm and settle this issue.

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1. Cai Z, Zhao B, Deng Y et al. Notch signaling in cerebrovascular diseases (Review). Mol Med Rep 2016; 14: 2883-98.
2. Crocco TJ, Goldstein JN. Stroke. In: Rosen’s Emergency Medicine. Philadelphia: Elsevier: 2014. p. 1363‑74.
3. Sacco RL, Kasner SE, Broderick JP et al. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44: 2064-89.
4. Vetrano DL, Landi F, De Buyser SL et al. Predictors of length of hospital stay among older adults admitted to acute care wards: a multicentre observational study. Eur J Intern Med 2014; 25: 56-62.
5. Dezmalj-Grbelja L, Bosnjak J, Lovrencić-Huzjan A, Ivica M, Demarin V. Moyamoya disease in a patient with brain tumor: case report. Acta Clin Croat 2010; 49: 459-63.
6. Di Napoli M, Shah IM. Neuroinflammation and cerebrovascular disease in old age: a translational medicine perspective. J Aging Res 2011; 2011: 857484.
7. Offner H, Subramanian S, Parker SM, Afentoulis ME, Vandenbark AA, Hurn PD. Experimental stroke induces massive, rapid activation of the peripheral immune system. J Cereb Blood Flow Metab 2006; 26: 654-65.
8. Amaro S, Chamorro Á. Translational stroke research of the combination of thrombolysis and antioxidant therapy. Stroke 2011; 42: 1495-9.
9. Fisher M. New approaches to neuroprotective drug development. Stroke 2011; 42: 24-7.
10. Intiso D, Zarrelli MM, Lagioia G et al. Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic stroke patients. Neurol Sci 2004; 24: 390-6.
11. Brabers NA, Nottet HS. Role of the proinflammatory cytokines TNF-alpha and IL-1beta in HIV-associated dementia. Eur J Clin Invest 2006; 36: 447-58.
12. 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 Res 2005; 1034: 11-24.
13. Tuttolomondo A, Di Raimondo D, di Sciacca R, Pinto A, Licata G. Inflammatory cytokines in acute ischemic stroke. Curr Pharm Des 2008; 14: 3574- 89.
14. Makwana M, Jones LL, Cuthill D et al. Endogenous transforming growth factor beta 1 suppresses inflammation and promotes survival in adult CNS. J Neurosci 2007; 27: 11201-13.
15. Lehrmann E, Kiefer R, Christensen T et al. Microglia and macrophages are major sources of locally produced transforming growth factor‐β1 after transient middle cerebral artery occlusion in rats. GLIA 1998; 24: 437-48.
16. Pang L, Ye W, Che XM, Roessler BJ, Betz AL, Yang GY. Reduction of inflammatory response in the mouse brain with adenoviral-mediated transforming growth factor-ss1 expression. Stroke 2001; 32: 544-52.
17. Gökdemir GS, Gökdemir MH, Karakılçık AZ. Total Oxidative Stress, Total Antioxidant Status and Erythrocytes Status in Patients with Acute Ischemic Stroke. Acta Med Mediterr 2017, 33: 157.
18. Gökdemir MT, Kaya H, Söğüt O, Kaya Z, Albayrak L, Taşkın A. The role of oxidative stress and inflammation in the early evaluation of acute nonST-elevation myocardial infarction: an observational study. Anadolu Kardiyol Derg 2013; 13: 131-6.
19. Söğüt Ö, Kaya H, Gökdemir MT et al. Early oxidative status in adult patients with isolated traumatic brain injury. Turk J Med Sci 2012; 42: 1010-9.
20. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37: 277-85.
21. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103-11.
22. Ahmad M, Graham SH. Inflammation after stroke: mechanisms and therapeutic approaches. Transl Stroke Res 2010; 1: 74-84.
23. Rodríguez-Yáñez M, Castillo J. Beyin iskemisinde inflamasyon belirteçlerinin rolü. Turkiye Klinikleri J Neur 2010; 5: 39-44.
24. Şahan M, Satar S, Koç AF, Sebe A. İskemik inme ve akut faz reaktanları. Arşiv Kaynak Tarama Dergisi 2014; 19: 84-140.
25. Demir H, Onur OE, Denizbaşı AA. Travmatik beyin hasarında inflamatuvar sitokinlerin rolü. Marmara Med J 2012; 25: 114-7.
26. Ashour WMR, Al-Anwa AD, Kamel AE, Aidaros MA. Predictors of early infection in cerebral ischemic stroke. J Med Life 2016; 9: 163-9.
27. Haeusler KG, Schmidt WU, Föhring F et al. Cellular immunodepression preceding infectious complications after acute ischemic stroke in humans. Cerebrovasc Dis 2008; 25: 50-8.
28. Vogelgesang A, Dressel A. Immunological consequences of ischemic stroke: Immunosuppression and autoimmunity. J Neuroimmunol 2011; 231:103-10.
29. Oto J, Suzue A, Inui D et al. Plasma proinflammatory and anti-inflammatory cytokine and catecholamine concentrations as predictors of neurological outcome in acute stroke patients. J Anesth 2008; 22: 207-12.
30. Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. Nat Rev Immunol 2005; 5: 629-40.
31. Licata G, Tuttolomondo A, Di Raimondo D, Corrao S, Di Sciacca R, Pinto A. Immunoinflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke. Thromb Haemost 2009; 101: 929- 37.
32. Masada T, Hua Y, Xi G, Yang GY, Hoff JT, Keep RF. Attenuation of intracerebral hemorrhage and thrombin-induced brain edema by overexpression of interleukin-1 receptor antagonist. J Neurosurg 2001; 95: 680-6.
33. Zeng L, Wang Y, Liu J et al. Pro-inflammatory cytokine network in peripheral inflammation response to cerebral ischemia. Neurosci Lett 2013; 548: 4-9.
34. Doyle KP, Cekanaviciute E, Mamer LE, Buckwalter MS. TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke. J Neuroinflammation 2010; 7: 62.
35. Kaestner S, Dimitriou I.TGF beta1 and TGF beta2 and their role in posthemorrhagic hydrocephalus following SAH and IVH. J Neurol Surg A Cent Eur Neurosurg 2013; 74: 279-84.
36. Logan A, Green J, Hunter A, Jackson R, Berry M. Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor-beta2. Eur J Neurosci 1999; 11: 2367-74.
37. Pál G, Vincze C, Renner É et al. Time course, distribution and cell types of induction of transforming growth factor betas following middle cerebral artery occlusion in the rat brain. PLoS One 2012; 7: 46731.
38. Al-Maghrebi M, Renno WM. Genistein alleviates testicular ischemia and reperfusion injury-induced spermatogenic damage and oxidative stress by suppressing abnormal testicular matrix metalloproteinase system via the Notch 2/Jagged 1/Hes-1 and caspase-8 pathways. J Physiol Pharmacol 2016; 67: 129-37.
39. Xie H, Sun J, Chen Y, Zong M, Li S, Wang Y. EGCG attenuates uric Acid-Induced inflammatory and oxidative stress responses by medicating the NOTCH pathway. Oxid Med Cell Longev 2015; 2015: 214836.