AKUT İSKEMİK İNMELİ HASTALARDA IL-18 VE ADROPİN DÜZEYLERİ

Year 2022, Volume: 29 Issue: 2, 187 - 195, 30.06.2022

Alper Eren , İbrahim İyigün

https://doi.org/10.17343/sdutfd.1002269

Abstract

Amaç
İnmeli hastalarda disfonksiyonel vasküler olaylara yol
açan önde gelen faktörlerden bir tanesi olan ateroskleroz;
endotelyal disfonksiyon ve vasküler inflamasyonun
önemli bir rol oynadığı çok faktörlü ve kompleks
bir süreçtir. Biz bu çalışmada endotel disfonksiyonu
ve inflamatuar süreçlerle ilişkisi gösterilmiş olan IL-
18 ve adropininin akut iskemik inme hastalarındaki
serum düzeyleri ile epidemiyolojik, klinik, radyolojik
bulgular ve inme şiddeti arasındaki ilişkiyi araştırmayı
amaçladık.
Gereç ve Yöntem
Çalışmamıza akut iskemik inme tanısı konulan 61
hasta ve kontrol grubu olarak 30 sağlıklı birey alındı.
Hasta grubunda etiyolojik ve klinik olarak inme alt
grupları ve inme şiddeti belirlendi. Hasta grubundan
ilk 24 saatte, kontrol grubundan herhangi bir zamanda
venöz kan örnekleri alınarak serumları ayrıldı ve
-80⁰C’de saklandı. ELISA yöntemi kullanılarak IL-8 ve
adropin düzeyleri belirlendi. Hasta ve kontrol gruplarının
IL-18 ve adropin düzeyleri ile iskemik inme arasındaki
ilişkiler istatistiksel olarak analiz edildi.
Bulgular
Adropin düzeyi hasta grubunda kontrol grubuna göre
istatistiksel olarak anlamlı derecede düşüktü (sırasıyla
398.01±403.51 ve 509.42±1492.89; p=0.041). Çalışma
ve kontrol gruplarının IL-18 düzeyleri benzerdi
(sırasıyla 24.87±14.26 ve 21.11±14.93; p=0.112).
İnme risk faktörleri, inme alt grupları ve inme şiddeti
ile belirlenen IL-18 ve adropin düzeyleri arasında ilişki
yoktu.
Sonuç
Bu bulgular, düşük adropin düzeylerinin ateroskleroz
göstergesi olarak iskemik inme risk tahmini ölçeklerinde
kullanılabileceğini göstermiştir. Akut iskemik inmeli
hasta grubu ile kontrol grubu arasında ortalama
serum IL-18 düzeyi açısından fark olmaması, IL-18'in
iskemiye bağlı inflamasyonda geç dönem bir sitokin
olarak rol oynayabileceğini düşündürmüştür.

Keywords

iskemik inme, adropin, IL-18, inflamasyon, endotel disfonksiyonu

Supporting Institution

Yok

Project Number

Tez no: 462412

Thanks

Atatürk Üniversitesi Tıp Fakültesi Tıbbi Biyokimya AD öğretim üyesi Prof. Dr. Ahmet KIZILTUNÇ hocama makalemin fikir ve labaoratuar aşamasındaki her türlü desteği için çok teşekkür ediyorum.

IL-18 AND ADROPIN LEVELS IN PATIENTS WITH ACUTE ISCHEMIC STROKE

Abstract

Objective
Atherosclerosis, one of the prominent factors causing
dysfunctional vascular events in stroke patients,
is a multi-factorial and complex process in which
endothelial dysfunction and vascular inflammation
play significant roles. This study aimed to investigate
the relationships between serum levels of IL-18 and
adropin, associated with endothelial dysfunction and
inflammatory processes in acute ischemic stroke
patients, with epidemiological, clinical, radiological
findings and stroke severity.
Materials and Methods
Sixty-one patients diagnosed with acute ischemic
stroke and 30 healthy individuals were included in the
study as the patient and control groups. In the patient
group, the stroke sub-groups and severity were
determined etiologically and clinically. Venous blood
samples were obtained within the first 24 hours in the
patient group, and at any time in the control group,
their serums were separated and stored at -80°C. IL-8
and adropin levels were determined using the ELISA
method. The relationships between patient and
control groups’ IL-18 and adropin levels and ischemic
stroke were analyzed statistically.
Results
The adropin level was statistically significantly
lower in the patient group than the control group
(398.01±403.51 and 509.42±1492.89, respectively;
p=0.041). The IL-18 levels of the study and control
groups were similar (24.87±14.26 and 21.11±14.93,
respectively; p=0.112). There was no relationship
between the IL-18 and adropin levels determined
with stroke risk factors, stroke sub-groups, and stroke
severity.
Conclusion
These results showed that low adropin levels could be
used to indicate atherosclerosis in the risk prediction
scales of ischemic stroke. The absence of a difference
between the patient group with acute ischemic stroke
and the control group regarding the first 24-hour mean
serum IL-18 level suggested that IL-18 could play
a role as a late-stage cytokine in ischemia-related
inflammation.

Keywords

ischemic stroke, adropin, IL-18, inflammation, endothelial dysfunction

Project Number

Tez no: 462412

References

• 1. Monica, W. H. O. & Project Principal Investigators. The World Health Organization MONICA project (monitoring trends and determinants in cardiovascular disease): a major international collabaration. Journal of clinical epidemiology. Oxford; New York: Pergamon Press 1988; vol. 41, no. 2.
• 2. Ihle-Hansen H, Thommessen B, Wyller TB, Engedal K, Fure B. Risk factors for and incidence of subtypes of ischemic stroke. Functional neurology 2012; 27: 1-35.
• 3. Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 2003; 4(5): 399-415.
• 4. Basic Kes V, Simundic AM, Nikolac N, et al. Pro- inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome. Clin Biochem. 2008; 41(16-17): 1330-4.
• 5. Dinarello CA. Novel targets for interleukin 18 binding protein. Ann Rheum Dis. 2001; 60[Suppl 3]:18–24.
• 6. Gürkaş E, Orhan G, Ak F. The relationship of IL-18 levels with early and late clinical findings and infarct volume in patients with acute ischemic stroke. Turkish Journal of Cerebrovascular Diseases 2012; 18(1): 10-15.
• 7. Mallat Z, Corbaz A, Scoazec A, et al. Expression of interleukin- 18 in human atherosclerotic plaques and relation to plaque instability. Circulation 2001; 104: 1598 –1603.
• 8. Blankenberg S, Luc G, Ducimetiere P, et al. Interleukin-18 and risk of coronary heart disease in European men: The Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation 2003; 108: 2453– 2459.
• 9. Stott DJ, Welsh P, Rumley A, et al. Adipocytokines and risk of stroke in older people: a nested case-control study. Int J Epidemiol. 2009; 38:253–61.
• 10. Zaremba J, Losy J. Interleukin-18 in acute ischaemic stroke patients. Neurol Sci. 2003; 24:117–24.
• 11. Sarchielli P, Nardi K, Chiasserini D, et al. Immunological profile of silent brain infarction and lacunar stroke. PLoS One. 2013; 8(7):e68428.
• 12. Bossù P, Salani F, Cacciari C, et al. Disease outcome, alexithymia and depression are differently associated with serum IL-18 levels in acute stroke. Curr Neurovasc Res. 2009; 6:163–70.
• 13. Yu XH, Qian K, Jiang N, et al. ABCG5/ABCG8 in cholesterol excretion and atherosclerosis. Clin. Chim. Acta 2014; 428: 82–88.
• 14. Kumar KG, Trevaskis JL, Lam DD, et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008;8:468–81.
• 15. Shahjouei S, Ansari S, Pourmotabbed T, Zand R. Potential roles of adropin in central nervous system: review of current literature. Front. Mol. Biosci. 2016; 3: 25.
• 16. Lovren F, Pan Y, Quan A, et al. Adropin is a novel regulator of endothelial function. Circulation 2010; 122 (11 Suppl. 1): 185- 192.
• 17. Kathir K, Adams MR. Endothelial dysfunction as a predictor of acute coronary syndromes. Semin Vasc Med. 2003;3:355–62.
• 18. Wu L, Fang J, Chen L, et al. Low serum adropin is associated with coronary atherosclerosis in type 2 diabetic and non-diabetic patients. Clin Chem Lab Med. 2014;52:751–8.
• 19. Topuz M, Celik A, Aslantas T, at al. Plasma adropin levels predict endothelial dysfunction like flow-mediated dilatation in patients with type 2 diabetes mellitus. J. Investig. Med. 2013; 61 (8): 1161–1164.
• 20. Esper RJ, Nordoby RA, Vilarino JO, et al. Endothelial dysfunction: a comprehensive appraisal. Cardiovasc Diabetol 2006; 5: 4.
• 21. Zhang C, Zhao L, Xu W, et al. Correlation of serum adropin level with coronary artery disease. Zhonghua Yi Xue Za Zhi 94 2014; 94(16): 1255–1257.
• 22. Yu HY, Zhao P, Wu MC, et al. Serum adropin levels are decreased in patients with acute myocardial infarction. Regul. Pept. 2014; 190–191: 46–49.
• 23. Gunaydin M, Aygun A, Usta M, at al. Serum adropin levels in patients with acute ischemic stroke. Medicine 2019; 8(3): 698- 702.
• 24. Yang C, DeMars KM, Candelario-Jalil E. Abstract TP277: Adropin is Profoundly Neuroprotective in Experimental Ischemic Stroke. Stroke 2017; 48(suppl_1), ATP277-ATP277.
• 25. Yang C, Sanz BD, DeMars KM, at al. Abstract WP315: Neuroprotective Effects of Endogenous Adropin in Experimental Ischemic Stroke. Stroke 2020; 51(Suppl_1), AWP315- AWP315.
• 26. Georgakis MK, Gill D, Rannikmäe K, at al. Genetically Determined Levels of Circulating Cytokines and Risk of Stroke. Circulation. 2019; 139:256–68.
• 27. Yuen CM, Chiu CA, Chang LT, et al. Level and value of interleukin- 18 after acute ischemic stroke. Circ J. 2007; 71(11): 1691-6.
• 28. Ormstad H, Aass HCD, Lund-Sørensen N, at al. Serum levels of cytokines and C-reactive protein in acute ischemic stroke patients, and their relationship to stroke lateralization, type, and infarct volume. Journal of neurology 2011; 258(4): 677-685.
• 29. Hao Y, Ding J, Hong R, at al. Increased interleukin-18 level contributes to the development and severity of ischemic stroke. Aging (Albany NY) 2019; 11(18): 7457.
• 30. Jander S, Schroeter M, Stoll G. Interleukin-18 expression after focal ischemia of the rat brain: association with the late-stage inflammatory response. J Cereb Blood Flow Metab 2002; 22: 62–70.
• 31. Wheeler RD, Boutin H, Touzani O, et al. No Role for Interleukin- 18 in Acute Murine Stroke-Induced Brain Injury. J Cereb Blood Flow Metab 2003; 23(5): 531-5.