Serum Inflammatory Cytokines (IL-6, TNF-α, and IL-1β) as Predictors of Disease Severity in Acute Ischemic Stroke Patients: A Cross-Sectional study
Inflammatory Cytokines in Acute Ischemic Stroke
DOI:
https://doi.org/10.69750/dmls.03.03.0194Keywords:
Acute ischemic stroke, IL-6, TNF-α, IL-1β, inflammation, NIHSS, biomarkersAbstract
Background: Acute ischemic stroke (AIS) is a major cause of mortality and long-term disability worldwide. Inflammation plays a critical role in the pathogenesis and progression of cerebral ischemic injury. Following arterial occlusion, several pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), are released and may reflect the severity of neuronal damage.
Objective: To evaluate the relationship between serum IL-6, TNF-α, and IL-1β levels and clinical severity in patients with acute ischemic stroke.
Methods: This cross-sectional study was conducted at the Department of Medicine, Nishtar Medical University, Multan, from June 2024 to June 2025. A total of 100 patients with acute ischemic stroke confirmed by CT or MRI within 24 hours of symptom onset were included. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Serum IL-6, TNF-α, and IL-1β levels were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analysis included one-way ANOVA, Pearson correlation, and multivariate logistic regression.
Results: Patients with severe stroke had significantly higher mean serum levels of IL-6, TNF-α, and IL-1β compared to mild and moderate stroke groups (p < 0.001). IL-6 showed the strongest positive correlation with NIHSS score (r = 0.68), followed by TNF-α (r = 0.61) and IL-1β (r = 0.55). Multivariate analysis identified IL-6 (AOR = 3.2), TNF-α (AOR = 2.8), and IL-1β (AOR = 2.3) as independent predictors of severe stroke.
Conclusion: Elevated inflammatory cytokines are significantly associated with AIS severity and may aid in early prognostic assessment.
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Abuhassan Q, Saeed TN, Al-Hussainy AF, Patel JR, Jamuna KV, Tripathi V, et al. Beyond cholesterol: targeting inflammatory biomarkers in cardiovascular disease. Clin Chim Acta. 2026; 588:120966. doi: 10.1016/j.cca.2026.120966
Wang X, Zhang X, Lin J, Lin P. Interleukin 6 and ischemic stroke: from mechanisms to clinical prospects. Mol Med Rep. 2026; 33:80. doi:10.3892/mmr.2026.13790
Bilal O, Omar AS, Tbishat L, Al-Subu A, Al-Qudah Z, Al-Hadidi A, et al. Pro-inflammatory cytokines in response to systemic inflammatory response syndrome post extra-corporeal membrane oxygenator decannulation. Int J Artif Organs. 2026;49(1):30-38. doi:10.1177/03913988251398846
Hua M, Chen WY, Ma AJ, et al. Circulating follistatin-like 1 associates with inflammation, cognitive decline, and amyloid pathology in Alzheimer’s disease and promotes Aβ-induced neuronal ferroptosis via PI3K/Akt signaling. Eur J Med Res. 2026; 31:468. doi:10.1186/s40001-026-04341-9
El-Rasool AOR, Badr MY, Farghal EE. Cranial ultrasonography and circulatory markers of inflammation as predictors for atherosclerosis in patients with depression. Egypt J Neurol Psychiatry Neurosurg. 2026; 62:16. doi:10.1186/s41983-026-01076-6
Mohammed YKA, Ahmed MA, Hassanein KM, et al. Ischemic stroke and inflammatory markers: a case-control study. Egypt J Neurol Psychiatry Neurosurg. 2025; 61:90. doi:10.1186/s41983-025-01017-9
Zhong C, Han Q, Yang L, Liu X, Zhang H, Chen W, et al. Correlations of levels of peripheral blood inflammatory cytokines and serum lipoprotein-associated phospholipase-A2 with acute ischemic stroke and their early prognostic value. J Interferon Cytokine Res. 2025;45(5):184-195. doi:10.1089/jir.2024.0176
Iordache MP, Buliman A, Costea-Firan C, Gligore TCI, Cazacu IS, Stoian M, et al. Immunological and inflammatory biomarkers in the prognosis, prevention, and treatment of ischemic stroke: a review of a decade of advancement. Int J Mol Sci. 2025;26(16):7928. doi:10.3390/ijms26167928
Zha X, Liu M, Ruan S, et al. Relationship between serum vitamin D levels and pro-inflammatory cytokines in patients with rheumatoid arthritis combined with cardiovascular disease. Clin Rheumatol. 2025; 44:3467-3475. doi:10.1007/s10067-025-07587-6
Zhang Y, Wang Z, Hu Q, et al. Upregulation of lncRNA CASC2 alleviates neuroinflammation in acute ischemic stroke and exhibits protective effects by targeting miR-155. Eur J Med Res. 2025;30:1247. doi:10.1186/s40001-025-03391-9
Altyar AE, Bhardwaj S, Ghaboura N, Kaushik P, Alenezi SK, Mantargi MJS, et al. Role of IL-2, IL-6, and TNF-α as potential biomarkers in ischemic heart disease: a comparative study of patients with CAD and non-CAD. Med Sci (Basel). 2025;13(2):40. doi:10.3390/medsci13020040
Qi S, Huang S, Qian R. Predictive value of combined serum nuclear factor erythroid 2-related factor 2 and prognostic nutritional index for sepsis after percutaneous nephrolithotomy. J Endourol. 2025;39(3):222-230. doi:10.1089/end.2024.0519
Pacinella G, Ciaccio AM, Casuccio A, Daidone M, Pecoraro R, Di Bona D, et al. Genetic polymorphisms and cytokine levels in ischemic stroke: associations with subtypes and prognosis. Expert Rev Clin Immunol. 2025;21(7):961-976. doi:10.1080/1744666X.2025.2517164
Li S, Geng K, Yang L, Zhang Y, Tao X, Cai J, et al. Correlation analysis between serum NLRP1 inflammasome and depression in acute stage of stroke. Neuroimmunomodulation. 2025;32(1):150-160. doi:10.1159/000546439
Hao Z, Ma D, Wu Y, Cao J, Wang W. Impact of inflammatory factors on coronary CT calcification score: correlation with plaque stability and evaluation of diagnostic efficiency. Am J Transl Res. 2025;17(11):9022-9031. doi:10.62347/BDUM2830
Peng B, Wang R, Jiang W, Zou M, Li H, Zhang H. Edaravone dexborneol in acute ischemic stroke patients treated with combined intravenous thrombolysis and mechanical thrombectomy for large vessel occlusion. Front Neurol. 2025;16:1681859. doi:10.3389/fneur.2025.1681859
Tian W, Cao H, Li X, et al. Adjunctive PCSK9 inhibitor evolocumab in the prevention of early neurological deterioration in non-cardiogenic acute ischemic stroke: a multicenter, prospective, randomized, open-label clinical trial. CNS Drugs. 2025;39:197-208. doi:10.1007/s40263-024-01145-5
Guo G, Xiao J, Chen J, Zhu C, Zhang Q, Li F. The correlation study of bone metabolism and inflammatory markers with major adverse cardiovascular events in patients with obstructive sleep apnea syndrome. J Inflamm Res. 2025;18:15817-15831. doi:10.2147/JIR.S538725
Pan Y, Fan F, Jiang J, et al. Clinical outcomes of anti-inflammatory therapies inhibiting the NLRP3/IL-1β/IL-6/CRP pathway in coronary artery disease patients: a systemic review and meta-analysis of 37,056 individuals from 32 randomized trials. Inflamm Res. 2025;74:99. doi:10.1007/s00011-025-02058-9
Li X, Xie X, Cheng S, Luo S, Zhu Y, Wu K. Predictive value of serum inflammatory factors and FT3 for stroke-associated pneumonia in patients with acute ischemic stroke. Neurologist. 2025;30(2):69-74. doi:10.1097/NRL.0000000000000570
Zhao H, Li W, Xu Q, Chen P, Wang X. Early Th1-Th2 cytokine imbalance as a predictor for post-stroke depression at 3 months. J Affect Disord. 2025;389:119650. doi:10.1016/j.jad.2025.119650
Bianchi J, Duarte FO, Camillo L, et al. Cluster analysis reveals distinct inflammatory phenotypes in cardiometabolic disease. Cardiovasc Diabetol Endocrinol Rep. 2025;11:15. doi:10.1186/s40842-025-00227-7
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