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Exploring causal association between circulating inflammatory cytokines and functional outcomes following ischemic
Huacong Liu1, Zhaoxing Liu1,2, Yumeng Huang1,2
1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
European Journal of Neurology
|November 14, 2023
Summary
This study reveals a causal link between inflammation and poor outcomes after ischemic stroke (IS). Elevated RANTES (CCL5) and EOTAXIN (CCL11) may worsen IS outcomes, while IL-18 might be a consequence.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Observational studies suggest links between inflammatory cytokines and functional outcomes post-ischemic stroke (IS).
- The causal relationship between specific inflammatory cytokines and IS outcomes remains unclear.
Purpose of the Study:
- To investigate the causal association between 41 circulating inflammatory cytokines and functional outcomes following IS using Mendelian randomization.
- To identify potential upstream and downstream inflammatory factors influencing IS recovery.
Main Methods:
- Two-sample bidirectional Mendelian randomization (MR) analysis.
- Utilized genome-wide association study (GWAS) data for 41 inflammatory cytokines (n=8293) and IS functional outcomes (n=6021) from European ancestry cohorts.
Main Results:
- Genetically predicted higher levels of RANTES (CCL5) and EOTAXIN (CCL11) were associated with increased adverse functional outcomes (mRS≥3) post-IS.
- Interleukin 18 (IL-18) showed a potential causal link as a downstream consequence of adverse IS functional outcomes.
- No significant causal relationships were found for other tested inflammatory cytokines and IS outcomes.
Conclusions:
- This MR study provides evidence for a causal role of inflammation in adverse functional outcomes following IS.
- RANTES (CCL5) and EOTAXIN (CCL11) may act as upstream factors, whereas IL-18 may be a downstream effect in IS pathophysiology.
- Further research is needed to explore the predictive and therapeutic potential of these cytokines in IS management.
