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.
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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.
