Association Between Peripheral IL-6 Levels in the Acute Stage of Stroke and Poststroke Depression: A Systematic...

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.

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.

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: I² = 17%, p < 0.001).

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.