Association between Serum Innate Immunity-Related Inflammatory Markers and MRI Features of Cerebral Small Vessel Disease: A Systematic Review and Meta-analysis

Abstract

Cerebral small vessel disease (CSVD) is a microvascular disorder associated with endothelial dysfunction, blood–brain barrier disruption, and chronic immune inflammation. However, the relationships between circulating inflammatory markers and magnetic resonance imaging (MRI) features of CSVD remain unclear.

A systematic search of PubMed, Embase, Web of Science, Cochrane Library, CNKI, and Wanfang databases was conducted from inception to December 2025. Observational studies evaluating associations between serum inflammatory markers and MRI-defined CSVD features, including white matter hyperintensities (WMH), lacunar infarction (LI), and cerebral microbleeds (CMB), were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models.

Eighteen studies were included. Elevated interleukin-6 (IL-6) levels were significantly associated with LI (OR=1.53, 95% CI: 1.11–2.11) and CMB (OR=1.28, 95% CI: 1.06–1.55). Increased high-sensitivity C-reactive protein (hs-CRP) levels were significantly associated with WMH (OR=2.19, 95% CI: 1.18–4.07), LI (OR=1.97, 95% CI: 1.21–3.20), and CMB (OR=1.67, 95% CI: 1.37–2.04). Elevated fibrinogen (FIB) levels were significantly associated with WMH (OR=1.48, 95% CI: 1.21–1.80). In contrast, conventional C-reactive protein showed no significant association with CSVD imaging markers.

This meta-analysis demonstrates that elevated IL-6, hs-CRP, and FIB levels are associated with MRI features of CSVD, supporting the involvement of innate immune inflammation in CSVD pathophysiology. These markers may reflect chronic cerebral microvascular injury and endothelial dysfunction. However, causal relationships cannot be established, and further prospective studies are required.