Journal of inflammation research · 2026
Impact of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor on Immune-Inflammatory Responses in the Acute Phase of Ischemic Stroke.
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Li Zhenzhen, Sun Cong, Zhang Qing, Ji Lifan, Zhang Yiting, Li Shuo, Gu Mengmeng, Gao Jie, Huang Zhihui, Wang Meng, Zhou Junshan, Zhu Lin, Jiang Teng, Zhou Qing, Deng Qiwen
Аннотация
BACKGROUND: Acute ischemic stroke (AIS) triggers a complex systemic immune-inflammatory response. While proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provide significant lipid-lowering and pleiotropic anti-inflammatory effects, their impact on early peripheral inflammatory and immune responses in AIS patients due to large artery atherosclerosis (LAA) remains underexplored.
METHODS: A total of 72 AIS patients attributed to LAA were included in the final analysis of this prospective study (the standard treatment group, n = 24; the intensive treatment group, n = 48). Fasting blood samples were obtained at admission and the 2-week follow-up. A comprehensive panel of laboratory parameters was assessed at baseline and the 2-week follow-up, encompassing lipid profiles, a spectrum of inflammatory biomarkers (including but not limited to high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)), and lymphocyte subsets.
RESULTS: The intensive treatment group achieved a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) compared to the standard treatment group (P < 0.001). Notably, the intensive treatment group also showed significant reductions in key pro-inflammatory cytokines IL-6 (P = 0.024) and TNF-α (P = 0.041). However, no significant between-group differences were observed in the changes of peripheral blood lymphocyte subsets (P > 0.050).
CONCLUSION: In AIS patients, early adjunctive PCSK9 inhibitor therapy provides superior lipid-lowering and may modulate specific pro-inflammatory cytokines compared to statin monotherapy, without significantly altering peripheral lymphocyte subset distributions within 2 weeks. Further large-scale studies are warranted to validate its immunomodulatory role and long-term clinical outcomes.
TRIAL REGISTRATION: ClinicalTrials.gov NCT05410457. Registered May 24, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05410457; ClinicalTrials.gov NCT05397405. Registered May 23, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05397405.
METHODS: A total of 72 AIS patients attributed to LAA were included in the final analysis of this prospective study (the standard treatment group, n = 24; the intensive treatment group, n = 48). Fasting blood samples were obtained at admission and the 2-week follow-up. A comprehensive panel of laboratory parameters was assessed at baseline and the 2-week follow-up, encompassing lipid profiles, a spectrum of inflammatory biomarkers (including but not limited to high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)), and lymphocyte subsets.
RESULTS: The intensive treatment group achieved a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) compared to the standard treatment group (P < 0.001). Notably, the intensive treatment group also showed significant reductions in key pro-inflammatory cytokines IL-6 (P = 0.024) and TNF-α (P = 0.041). However, no significant between-group differences were observed in the changes of peripheral blood lymphocyte subsets (P > 0.050).
CONCLUSION: In AIS patients, early adjunctive PCSK9 inhibitor therapy provides superior lipid-lowering and may modulate specific pro-inflammatory cytokines compared to statin monotherapy, without significantly altering peripheral lymphocyte subset distributions within 2 weeks. Further large-scale studies are warranted to validate its immunomodulatory role and long-term clinical outcomes.
TRIAL REGISTRATION: ClinicalTrials.gov NCT05410457. Registered May 24, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05410457; ClinicalTrials.gov NCT05397405. Registered May 23, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05397405.