Murat ÇAKIR, Seda SABAH ÖZCAN, Hikmet SAÇMACI

Negative correlation between TNF-α and triglyceride levelsin patients with cerebral infarction

Aim: To investigate the interactions between tumor necrosis factor-alpha (TNF-α) and blood lipid levels in patients with acute cerebral infarction.Materials and Methods: A total of 43 cerebral infarction patients who applied to the neurology and emergency department of our faculty were included in cross-sectional matched case-control study, and the results were compared with 41 controls who had similar age and comorbidities. In addition to fasting serum lipids, serum glucose, C-reactive protein and hemogram were analyzed as well. Classification of infarct was made. An enzyme-linked immunosorbent test was used to determine baseline plasma TNF-α levels at the time of first admission and potential correlations between the groups were analyzed.Results: Compared to the control group, the cerebral ischemia group had a higher median TNF-α level (23.53; range, 21.74-43.29 ng/L vs. 23.00; range, 20.62-37.34 ng/L); however, the difference was not significant (p > 0.05). Groups were similar regarding blood lipid values (p > 0.05). In the patient group, TNF-α level showed a negative correlation with triglyceride (TG) and TG / HDL cholesterol (HDL-C) (rho= -0.319 p= 0.037 and rho= -0.321 p= 0.036), whereas no significant correlation was determined in the control group (p > 0.05), on the other hand plasma level of TNF-α was positively correlated with the National Health Stroke Scale score (rho = 0.455 p = 0.002).Conclusions: Our cross-sectional study revealed an interaction between decreased TG and TG / HDL-C and a high concentration of TNF-α in cerebral infarction for the first time. The importance of our finding is that it provides useful preliminary information, which is necessary for further research in this field.

PDF

___

1. Shan Y, Hu J, Lv H, et al. miR-221 Exerts Neuroprotective Effects in Ischemic Stroke by Inhibiting the Proinflammatory Response. J Stroke Cerebrovasc Dis 2021;30:105489.
2. Roth S, Yang J, Cramer JV, et al. Detection of cytokineinduced sickness behavior after ischemic stroke by an optimized behavioral assessment battery. Brain Behav Immun 2021;91:668-72.
3. Maida CD, Norrito RL, Daidone M, et al. Neuroinflammatory Mechanisms in Ischemic Stroke: Focus on Cardioembolic Stroke, Background, and Therapeutic Approaches. Int J Mol Sci 2020;21.
4. Postal M, Lapa AT, Sinicato NA, et al. Depressive symptoms are associated with tumor necrosis factor alpha in systemic lupus erythematosus. J Neuroinflammation 2016;13:1-7.
5. Lambertsen KL, Finsen B, Clausen BH. Post-stroke inflammation-target or tool for therapy? Acta Neuropathol 2019;137:693-714.
6. Lin SY, Wang YY, Chang CY, et al. TNF-α Receptor Inhibitor Alleviates Metabolic and Inflammatory Changes in a Rat Model of Ischemic Stroke 2021;10.
7. Pawluk H, Woźniak A, Grześk G. The Role of Selected Pro-Inflammatory Cytokines in Pathogenesis of Ischemic Stroke 2020;15:469-84.
8. Lasek-Bal A, Jedrzejowska-Szypulka H, Student S, et al. The importance of selected markers of inflammation and blood-brain barrier damage for short-term ischemic stroke prognosis. J Physiol Pharmacol 2019;70.
9. Kloska A, Malinowska M, Gabig-Cimińska M, et al. Lipids and Lipid Mediators Associated with the Risk and Pathology of Ischemic Stroke. Int J Mol Sci 2020;21.
10. Chen X, Xun K, Chen L, et al. TNF-alpha, a potent lipid metabolism regulator. Cell Biochem Funct 2009;27:407-16.
11. Soeki T, Sata M. Inflammatory biomarkers and atherosclerosis. Int Heart J 2016:15-346.
12. Jiang Y, Dai M, Nie WJ, et al. Effects of the ethanol extract of black mulberry (Morus nigra L.) fruit on experimental atherosclerosis in rats. J Ethnopharmacol 2017;200:228-35.
13. Subramani C, Rajakkannu A, Rathinam A, et al. Anti-atherosclerotic activity of root bark of Premna integrifolia Linn. in high fat diet induced atherosclerosis model rats. J Pharm Anal 2017;7:123-8.
14. Wymann MP, Schneiter R. Lipid signalling in disease. Nat Rev Mol Cell Biol 2008;9:162-76.
15. Wytrykowska A, Prosba-Mackiewicz M, Nyka WM. IL-1β, TNF-α, and IL-6 levels in gingival fluid and serum of patients with ischemic stroke. J Oral Sci 2016;58:509-13.
16. Hahn BH, Grossman J, Ansell BJ, et al. Altered lipoprotein metabolism in chronic inflammatory states: proinflammatory high-density lipoprotein and accelerated atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther 2008;10:213.
17. Espinoza M, Aguilera A, Auxiliadora Bajo M, et al. Tumor necrosis factor alpha as a uremic toxin: correlation with neuropathy, left ventricular hypertrophy, anemia, and hypertriglyceridemia in peritoneal dialysis patients. Adv Perit Dial 1999;15:82-6.
18. Stepanova N, Driianska V, Savchenko S. Dyslipidemia and Intraperitoneal Inflammation Axis in Peritoneal Dialysis Patients: A Cross-Sectional Pilot Study. Kidney Dis (Basel) 2020;6:35-42.
19. Sumbria RK, Boado RJ, Pardridge WM. Brain protection from stroke with intravenous TNFα decoy receptorTrojan horse fusion protein. J Cereb Blood Flow Metab 2012;32:1933-8.
20. Emsley HC, Tyrrell PJ. Inflammation and infection in clinical stroke. J Cereb Blood Flow Metab 2002;22:1399-419.
21. Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci 2019;20:6008.
22. Zhao SP, Dong SZ. Effect of tumor necrosis factor alpha on cholesterol efflux in adipocytes. Clin Chim Acta 2008;389:67-71.
23. Chen DY, Chen YM, Hsieh TY, et al. Significant effects of biologic therapy on lipid profiles and insulin resistance in patients with rheumatoid arthritis. Arthritis Res Ther 2015;17:52.
24. Ehsani AH, Mortazavi H, Balighi K, et al. Changes in body mass index and lipid profile in psoriatic patients after treatment with standard protocol of infliximab. Acta Medica Iranica 2016:570-5.
25. Hassan S, Milman U, Feld J, et al. Effects of anti-TNF-α treatment on lipid profile in rheumatic diseases: an analytical cohort study. Arthritis Research & Therapy 2016;18:1-9.
26. Ferraz Filho AC, dos Santos LP, Silva MB, et al. Lipid profile and anti-TNF-α use. Revista Brasileira de Reumatologia (English Edition) 2013;53:444-7.
27. Shi J, Fan J, Su Q, et al. Cytokines and abnormal glucose and lipid metabolism. Front Endocrinol 2019;10:703.
28. Popa C, Netea MG, van Riel PL, et al. The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res 2007;48:751-62.
29. Clark IA, Vissel B. Broader Insights into Understanding Tumor Necrosis Factor and Neurodegenerative Disease Pathogenesis Infer New Therapeutic Approaches. J Alzheimers Dis 2021;79:931-48.
30. Patel R, Palit SP, Rathwa N, et al. Genetic variants of tumor necrosis factor-α and its levels: A correlation with dyslipidemia and type 2 diabetes susceptibility. Clin Nutr 2019;38:1414-22.