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Serum Interleukin-1 Levels Are Associated with Intracranial Aneurysm Instability

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Abstract

Serum interleukin-1 (IL-1) are possibly indicative of the inflammation in the intracranial aneurysm (IA) wall. This study aimed to investigate whether IL-1 could discriminate the unstable IAs (ruptured intracranial aneurysms (RIAs) and symptomatic unruptured intracranial aneurysms (UIAs)) from stable, asymptomatic UIAs. IA tissues and blood samples from 35 RIA patients and 35 UIA patients were collected between January 2017 and June 2020 as the derivation cohort. Blood samples from 211 patients with UIAs were collected between January 2021 and June 2022 as the validation cohort (including 63 symptomatic UIAs). Blood samples from 35 non-cerebral-edema meningioma patients (non-inflammatory control) and 19 patients with unknown-cause subarachnoid hemorrhage (hemorrhagic control) were also collected. IL-1β and IL-1.ra (IL-1 receptor antagonist) were measured in serum and IA tissues, and the IL-1 ratio was calculated as log10 (IL-1.ra/IL-1β). Based on the derivation cohort, multivariate logistic analysis showed that IL-1β (odds ratio, 1.48, P = 0.001) and IL-1.ra (odds ratio, 0.74, P = 0.005) were associated with RIAs. The IL-1 ratio showed an excellent diagnostic accuracy for RIAs (c-statistic, 0.91). Histological analysis confirmed the significant correlation of IL-1 between serum and aneurysm tissues. IL-1 ratio could discriminate UIAs from non-inflammatory controls (c-statistic, 0.84), and RIAs from hemorrhagic controls (c-statistic, 0.95). Based on the validation cohort, the combination of IL-1 ratio and PHASES score had better diagnostic accuracy for symptomatic UIAs than PHASES score alone (c-statistic, 0.88 vs 0.80, P < 0.001). Serum IL-1 levels correlate with aneurysm tissue IL-1 levels and unstable aneurysm status, and could serve as a potential biomarker for IA instability.

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Data Availability

The datasets generated and/or analyzed during the current study are not publicly available due to ethical requirement but are available from the corresponding author on reasonable request.

Abbreviations

IA:

Intracranial aneurysm

RIA:

Ruptured intracranial aneurysm

UIA:

Unruptured intracranial aneurysm

GSDMD:

Gasdermin D

IOD:

Integrated optical density

ICA:

Internal carotid artery

MCA:

Middle cerebral artery

IL-1:

Interleukin 1

IL-1β:

Interleukin 1 β

IL-1.ra:

Interleukin 1 receptor antagonist

CTA:

Computational tomographic angiography

CT:

Computational tomography

MRI:

Magnetic resonance image

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Funding

This study was supported by the “National Natural Science Foundation of China (Grant No. 82071296),” “National Key Research and Development Program of the 14th Five-Year Plan (Grant No. 2021YFC2501100),” “Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (Grant No.202014)” and “TAIHU Top Talent Support Program for Top Medical Experts (Grant No. TH202109).”

Author information

Author notes

  1. Qingyuan Liu and Peng Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Qingyuan Liu, Peng Liu, Yisen Zhang & Shuo Wang

  2. Department of Radiology, University of Washington, Seattle, Washington, USA

    Mahmud Mossa-Basha & Chengcheng Zhu

  3. Department of Neurosurgery, Duke University, Durham, North Carolina, USA

    David M. Hasan

  4. Department of Emergency, the Affiliated Wuxi NO.2 People’s Hospital of Jiangnan University, Wuxi, Jiangsu, China

    Jiangan Li & Shuo Wang

Authors
  1. Qingyuan Liu
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  2. Peng Liu
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Contributions

Author contributions to the study and manuscript preparation include the following. Conception and design: QY. Liu and P. Liu. Acquisition of data: QY. Liu, P. Liu, YS. Zhang, and JA. Li. Analysis and interpretation of data: QY. Liu and CC. Zhu. Drafting the article: QY. Liu. Critically revising the article: Mahmud. MB, David H, CC. Zhu, and S. Wang. Approving the final version of the manuscript on behalf of all authors: S. Wang. Study supervision: S. Wang.

Corresponding authors

Correspondence to Jiangan Li, Chengcheng Zhu or Shuo Wang.

Ethics declarations

Ethics Approval and Consent to Participate

This study was approved by institutional ethics committees (KY2017-076-01). All patients (or guardians of patients) provided written informed consents.

Consent for Publication

Not applicable.

Conflict of Interest

The authors declare no competing interests.

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Supplementary Information

Supplementary materials 1:

Supplemental Figure 1. Establishment of the derivation cohort. Supplemental Figure 2. Establishment of the validation cohort. Supplemental Figure 3. The representative cases of aneurysm wall remodeling. Supplemental Figure 4. The measurement of atherosclerosis area. Supplemental Figure 5. The back-to-back histograms presented the propensity score between pre- and post-PSM. Supplemental Figure 6. The correlation of IL-1 between serum and aneurysm samples. Supplemental Figure 7. Subgroup analysis to identify the correlation of IL-1 between serum and aneurysm samples. Supplemental Figure 8. The modified Fisher scaler between patients with RIAs and patients in hemorrhagic control. Supplemental Table 1. The reagents in this study. Supplemental Table 2. The propensity score between pre- and post-PSM within the derivation cohort. Supplemental Table 3. Inter-observer agreement analyses. Supplemental Table 4. The serum cytokines of RIA patients and UIA patients. Supplemental Table 5. The logistics regression for the serum cytokines associated with ruptured intracranial aneurysm. Supplemental Table 6. The comparison of characteristics among the derivation cohort, healthy control and hemorrhagic control. Supplemental Table 8. The characteristics of patients in the validation cohort. Supplemental Table 9. The univariate logistic analysis for factors associated with symptomatic UIAs. Supplemental Table 10. The multivariate logistics regression for factors associated with symptomatic UIAs.

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Liu, Q., Liu, P., Zhang, Y. et al. Serum Interleukin-1 Levels Are Associated with Intracranial Aneurysm Instability. Transl. Stroke Res. 15, 433–445 (2024). https://doi.org/10.1007/s12975-023-01140-w

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  • DOI: https://doi.org/10.1007/s12975-023-01140-w

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