ROLE OF INFLAMMATORY MARKER TNF-ALPHA AND IL-6 IN PATHOGENESIS OF STROKE

Abstract

Ischemic stroke (IS) is a leading cause of disability and mortality worldwide, disproportionately affecting populations in low- and middle-income countries (LMICs) such as Pakistan. Despite advances in diagnostics and therapeutics, the roles of inflammatory cytokines—particularly tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)—in the pathophysiology of IS remain incompletely understood. These cytokines are central to the neuroinflammatory cascade, influencing immune activation, neuronal survival, endothelial dysfunction, coagulation, and blood–brain barrier (BBB) integrity, with dual effects of exacerbating injury and promoting recovery. This observational case–control study aimed to evaluate serum TNF-α and IL-6 levels in patients with IS and compare them with individuals having dyslipidemia and healthy controls. A total of 210 participants were recruited and equally stratified into three groups (n = 70). ELISA findings demonstrated significantly higher levels of IL-6 in the stroke patients than in controls (p < 0.001), yet no group differences for TNF-α. Nonetheless, the correlation between TNF-α and IL-6 was highly positive (R² > 0.65), and this may imply that the cytokines share overlapping functions within neuroinflammatory mechanisms. Findings show IL-6 to be employed as a more stable biomarker of stroke severity while TNF-α can be an early but short-term responder. Elevated levels of cytokines were also reported to be related to modifiable risk factors such as obesity, hypertension, diabetes, and lifestyle and to the overall social determinants of socioeconomic status. viii These findings highlight the prognostic significance of IL-6 in IS and validate the merit of including inflammatory biomarkers in clinical risk scores. Cytokine imbalance modulation with immunomodulatory intervention could provide novel therapeutic options to minimize stroke morbidity and mortality, especially for LMIC patients.