Iranian Journal of Immunology

Increased Serum Levels of IL-1β after Ischemic Stroke are Inversely Associated with Vitamin D

Document Type : Short Communication

Authors

Mahnaz Bayat 1
Niloufar Razavi Moosavi 1
Najmeh Karimi 1, 2
Moosa Rahimi 3
Afshin Borhani-Haghighi 1, 4, 5

1 Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Laboratory of Basic Sciences, Mohammad Rasul Allah Research Tower, Shiraz University of Medical Sciences, Shiraz, Iran.

4 Department of Neurology, John Hunter Hospital, University of Newcastle, Newcastle, Australia.

5 Hunter Medical Research Institute and the University of Newcastle, Newcastle, Australia.

https://doi.org/10.22034/iji.2023.96384.2432
Abstract
Background: The initial inflammatory reaction starts following occlusion in ischemic stroke (IS). Interleukin-1β (IL-1β) is a pro-inflammatory cytokine with a crucial role in the pathogenesis of neurodegenerative disorders.
Objective: To investigate the levels of IL-1β and vitamin D (VitD) in patients with IS compared with controls and their correlation.
Methods: The serum level of 25-OH VitD and IL-1β was assessed in 102 IS patients (0-24 h after stroke) and 102 controls with an enzyme-linked immunosorbent assay (ELISA) kit.
Results: We found a significant increase in IL-1β (80.14±6.8 vs. 60.32±4.1 pg/ml, p<0.05) and a decrease in VitD level (24.3±1.4 vs. 29.9±1.5 ng/ml, p<0.01) in the IS patients compared with the controls. There was a significantly positive correlation between the National Institutes of Health Stroke Scale (NIHSS) and IL-1β according to both the Spearman correlation (r=0.35, p=0.0003) and the linear regression (beta=0.255, p=0.014). Also, a significant negative association between VitD and NIHSS was detected by the Spearman correlation (r=-0.41, p<0.0001) and the linear regression (beta=-0.381, p=0.000). Moreover, we found a significant negative correlation (r=-0.26, p=0.006) between the serum levels of VitD and IL-1β in the patient group.
Conclusion: Ischemic stroke correlates positively with IL-1β and negatively with VitD levels. The speculated role of VitD deficiency in the evolution and severity of stroke may be justified by its role in the modification of inflammation.

Keywords

Inflammation
Interleukin-1β
Ischemic Stroke
Vitamin D
  1. Tabrizi R, Lankarani KB, Kardeh B, Akbari H, Azarpazhooh MR, Borhani-Haghighi A. A Comprehensive Systematic Review and Meta-analysis on the Risk Factors of Stroke in Iranian Population. Arch Iran Med. 2021;24(1):64-77.
  2. safari A, safari, R., & Borhani-Haghighi, A. Immunology of stroke. Galen Medical Journal,. 2016;5( (51)):10-7.
  3. Doll DN, Barr TL, Simpkins JW. Cytokines: their role in stroke and potential use as biomarkers and therapeutic targets. Aging Dis. 2014;5(5):294-306.
  4. Nilupul Perera M, Ma HK, Arakawa S, Howells DW, Markus R, Rowe CC, et al. Inflammation following stroke. J Clin Neurosci. 2006;13(1):1-8.
  5. Ahn KS, Aggarwal BB. Transcription factor NF-kappaB: a sensor for smoke and stress signals. Ann N Y Acad Sci. 2005;1056:218-33.
  6. Ormstad H, Aass HC, Lund-Sorensen N, Amthor KF, Sandvik L. Serum levels of cytokines and C-reactive protein in acute ischemic stroke patients, and their relationship to stroke lateralization, type, and infarct volume. J Neurol. 2011;258(4):677-85.
  7. Tarkowski E, Rosengren L, Blomstrand C, Wikkelso C, Jensen C, Ekholm S, et al. Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke. 1995;26(8):1393-8.
  8. Shademan B, Nourazarian A, Laghousi D, Karamad V, Nikanfar M. Exploring potential serum levels of Homocysteine, interleukin-1 beta, and apolipoprotein B 48 as new biomarkers for patients with ischemic stroke. J Clin Lab Anal. 2021:e23996.
  9. Mazzotta G, Sarchielli P, Caso V, Paciaroni M, Floridi A, Floridi A, et al. Different cytokine levels in thrombolysis patients as predictors for clinical outcome. Eur J Neurol. 2004;11(6):377-81.
  10. Sotgiu S, Zanda B, Marchetti B, Fois ML, Arru G, Pes GM, et al. Inflammatory biomarkers in blood of patients with acute brain ischemia. Eur J Neurol. 2006;13(5):505-13.
  11. Wytrykowska A, Prosba-Mackiewicz M, Nyka WM. IL-1beta, TNF-alpha, and IL-6 levels in gingival fluid and serum of patients with ischemic stroke. J Oral Sci. 2016;58(4):509-13.
  12. Siniscalchi A, Lochner P, Anticoli S, Chirchiglia D, De Sarro G, Gallelli L. What is the Current Role for Vitamin D and the Risk of Stroke? Current neurovascular research. 2019;16(2):178-83.
  13. Safari A FN, Borhani-Haghighi A. The Association Between Inflammatory Biomarkers and Vitamin D Level With Evolution and Severity of Stroke. Basic and Clinical neuroscience.
  14. Williams LS, Yilmaz EY, Lopez-Yunez AM. Retrospective assessment of initial stroke severity with the NIH Stroke Scale. Stroke. 2000;31(4):858-62.
  15. Kwan J, Hand P. Early neurological deterioration in acute stroke: clinical characteristics and impact on outcome. QJM : monthly journal of the Association of Physicians. 2006;99(9):625-33.
  16. Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. 2020;75(6):1334-57.
  17. American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2004;27 Suppl 1:S5-S10.
  18. Adams HP, Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35-41.
  19. Balvers MG, Brouwer-Brolsma EM, Endenburg S, de Groot LC, Kok FJ, Gunnewiek JK. Recommended intakes of vitamin D to optimise health, associated circulating 25-hydroxyvitamin D concentrations, and dosing regimens to treat deficiency: workshop report and overview of current literature. J Nutr Sci. 2015;4:e23.
  20. Clausen BH, Wirenfeldt M, Hogedal SS, Frich LH, Nielsen HH, Schroder HD, et al. Characterization of the TNF and IL-1 systems in human brain and blood after ischemic stroke. Acta Neuropathol Commun. 2020;8(1):81.
  21. Emsley HC, Smith CJ, Gavin CM, Georgiou RF, Vail A, Barberan EM, et al. Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production. BMC Neurol. 2007;7:5.
  22. Kaneko N, Kurata M, Yamamoto T, Morikawa S, Masumoto J. The role of interleukin-1 in general pathology. Inflamm Regen. 2019;39:12.
  23. Nowrouzi-Sohrabi P, Kalani M, Izadpanah P, Ahmadvand H, Fakhour M, Fadaei R, et al. Vitamin D status influences cytokine production and MALAT1 expression from the PBMCs of patients with coronary artery disease and healthy controls. Rev Assoc Med Bras (1992). 2020;66(12):1712-7.
  24. Evans MA, Kim HA, Ling YH, Uong S, Vinh A, De Silva TM, et al. Vitamin D3 Supplementation Reduces Subsequent Brain Injury and Inflammation Associated with Ischemic Stroke. Neuromolecular medicine. 2018;20(1):147-59.
  25. Narasimhan S, Balasubramanian P. Role of Vitamin D in the Outcome of Ischemic Stroke- A Randomized Controlled Trial. J Clin Diagn Res. 2017;11(2):CC06-CC10.
  26. Kadri A, Sjahrir H, Juwita Sembiring R, Ichwan M. Combination of vitamin A and D supplementation for ischemic stroke: effects on interleukin-1ss and clinical outcome. Med Glas (Zenica). 2020;17(2):425-32.
  27. Di Rosa M, Malaguarnera M, Nicoletti F, Malaguarnera L. Vitamin D3: a helpful immuno-modulator. Immunology. 2011;134(2):123-39.
  28. Roffe-Vazquez DN, Huerta-Delgado AS, Castillo EC, Villarreal-Calderon JR, Gonzalez-Gil AM, Enriquez C, et al. Correlation of Vitamin D with Inflammatory Cytokines, Atherosclerotic Parameters, and Lifestyle Factors in the Setting of Heart Failure: A 12-Month Follow-Up Study. Int J Mol Sci. 2019;20(22).
  29. Chen Y, Zhang J, Ge X, Du J, Deb DK, Li YC. Vitamin D receptor inhibits nuclear factor kappaB activation by interacting with IkappaB kinase beta protein. J Biol Chem. 2013;288(27):19450-8.
  30. Nonn L, Peng L, Feldman D, Peehl DM. Inhibition of p38 by vitamin D reduces interleukin-6 production in normal prostate cells via mitogen-activated protein kinase phosphatase 5: implications for prostate cancer prevention by vitamin D. Cancer Res. 2006;66(8):4516-24.
  31. Rai V, Agrawal DK. Role of Vitamin D in Cardiovascular Diseases. Endocrinol Metab Clin North Am. 2017;46(4):1039-59.
  32. Wang Q, Zhu Z, Liu Y, Tu X, He J. Relationship between serum vitamin D levels and inflammatory markers in acute stroke patients. Brain Behav. 2018;8(2):e00885.
  33. Balden R, Selvamani A, Sohrabji F. Vitamin D deficiency exacerbates experimental stroke injury and dysregulates ischemia-induced inflammation in adult rats. Endocrinology. 2012;153(5):2420-35.
  34. Omidvar Rezaei MR, Mehrdad Roozbeh,Bahareh Fazeli, Mohammadreza Hajiesmaeili, Hossein Pakdaman, and Leila Simani. Does vitamin D administration play a role in outcome of patients with acute ischemic stroke? A randomized controlled trial. current journal of neurology. 2021;20(1):8-14.
  35. Zeng L, He X, Liu J, Wang L, Weng S, Wang Y, et al. Differences of circulating inflammatory markers between large- and small vessel disease in patients with acute ischemic stroke. Int J Med Sci. 2013;10(10):1399-405.
  36. Tuttolomondo A, Di Raimondo D, Pecoraro R, Arnao V, Pinto A, Licata G. Inflammation in ischemic stroke subtypes. Curr Pharm Des. 2012;18(28):4289-310.
  37. Licata G, Tuttolomondo A, Di Raimondo D, Corrao S, Di Sciacca R, Pinto A. Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke. Thromb Haemost. 2009;101(5):929-37.
Iranian Journal of Immunology
Volume 20, Issue 3
Summer 2023
Pages 359-367

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