Association Between Peripheral IL‐6 Levels in the Acute Stage of Stroke and Poststroke Depression: A Systematic Review and Meta‐Analysis

ABSTRACT Background Interleukin‐6 (IL‐6) has been reported to be associated with depression; however, whether higher peripheral levels of IL‐6 are associated with poststroke depression (PSD) remains controversial. To date, correlative meta‐analyses of the relationship between IL‐6 levels and PSD are lacking. Methods We performed a comprehensive search of databases to explore qualified studies reporting IL‐6 levels in the acute phase of stroke and PSD before November 2024. The standard mean deviation (SMD) and 95% confidence interval (CI) were calculated to detect differences in peripheral IL‐6 concentrations between PSD patients and non‐PSD patients. Results A total of 22 studies including 4928 participants were included in this meta‐analysis. The results revealed that PSD patients had significantly higher peripheral IL‐6 levels in the acute phase of stroke than non‐PSD patients did (SMD = 0.66, 95% CI = 0.42–0.90). Higher IL‐6 levels were detected in patients with PSD than in non‐PSD patients whether the assessment of depressive symptoms was conducted within 3 months or later, but not at the time of discharge (at discharge: SMD = 1.76, 95% CI: −0.42–3.94, p = 0.11; ≤ 3 months: SMD = 2.81, 95% CI: 1.50–4.12, p < 0.001; > 3 months: SMD = 3.17, 95% CI: 0.62–5.71, p < 0.05). The result of serum for measuring peripheral IL‐6 concentration was significant (SMD = 3.17, 95% CI = [1.63, 4.72], p < 0.001); however, plasma was not (SMD = 3.14, 95% CI = [−0.13, 6.40], p = 0.06). In addition, HAMD seemed to be more suitable for evaluating depressive symptoms than BDI‐FS (HAMD: SMD = 3.31, 95% CI = [1.86, 4.75], p < 0.001; BDI‐FS: SMD = 1.22, 95% CI = [−0.18, 2.62], p = 0.09). The sample collection time was the source of high heterogeneity (the subgroup of sample collection time within 1 day: I 2 = 17%, p < 0.001). Conclusion Higher peripheral IL‐6 concentrations in the acute stage of stroke are closely related to the risk of PSD; collecting samples within 1 day after stroke onset and evaluating depression post discharge are recommended.