Serum IL-1, Pyroptosis and Intracranial Aneurysm Wall Enhancement: Analysis Integrating Radiology, Serum Cytokines and Histology

Qingyuan Liu; Yisen Zhang; Chengcheng Zhu; Weiqi Liu; Xuesheng Ma; Jingang Chen; Shaohua Mo; Linggen Dong; Nuochuan Wang; Jun Wu; Peng Liu; Hongwei He; Shuo Wang

doi:10.3389/fcvm.2022.818789

Serum IL-1, Pyroptosis and Intracranial Aneurysm Wall Enhancement: Analysis Integrating Radiology, Serum Cytokines and Histology

Front Cardiovasc Med. 2022 Jan 27:9:818789. doi: 10.3389/fcvm.2022.818789. eCollection 2022.

Authors

Qingyuan Liu^{1

2}, Yisen Zhang^{3

4}, Chengcheng Zhu⁵, Weiqi Liu⁶, Xuesheng Ma⁶, Jingang Chen⁶, Shaohua Mo^{1

2}, Linggen Dong³, Nuochuan Wang⁷, Jun Wu¹, Peng Liu^{3

4}, Hongwei He^{3

4}, Shuo Wang^{1

2}

Affiliations

¹ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² China National Clinical Research Center for Neurological Diseases, Beijing, China.
³ Department of Neurointevention, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ Neurosurgical Institution, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁵ Department of Radiology, University of Washington, Seattle, WA, United States.
⁶ Medical Image Center, Tongxinyilian (Unimed), Tsinghua Tongfang Science and Technology Mansion, Beijing, China.
⁷ Department of Blood Transfusion, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Abstract

Background and purpose: Aneurysm wall enhancement (AWE) is correlated with the rupture and growth risk of unruptured intracranial aneurysms (UIAs). Pyroptosis is a proinflammation mode of lytic cell death, mediated by pyroptosis-related proteins, i.e., gasdermin D and interleukin 1 β (IL-1β). Integrating serum cytokines and histology, this study aimed to investigate the correlation between AWE and pyroptosis in UIAs.

Methods: UIA patients receiving microsurgical clipping were prospectively enrolled from January 2017 and June 2020. UIA samples were collected, as well as the corresponding blood samples. In this study, high-resolution magnetic resonance was employed to identify the AWE. The serum 46-cytokines examination and the histological analysis were conducted to determine pyroptosis, CD68 and MMP2. The IL-1 ra/beta ratio was determined by complying with the serum IL-1β and IL-1.ra. A comparison was drawn in the differences between UIAs with and without AWE. Lastly, the correlation between inflammation in UIA samples and serums was investigated.

Results: This study included 34 UIA patients. The serum proinflammatory cytokines [IL-1β (P < 0.001) and TNF-α (P < 0.001)] were up-regulated, and serum anti-inflammatory cytokine (IL-1.ra, P = 0.042) were down-regulated in patients with AWE UIAs. The patients with AWE UIAs achieved a higher IL-1.ra/beta ratio (P < 0.001). The multivariate logistic analysis demonstrated IL-1β [odds ratio (OR), 1.15; 95% confidence interval (CI), 1.02-1.30; P = 0.028] and IL-1.ra (OR, 0.998; 95% CI, 0.997-1.000; P = 0.017) as the risk factors correlated with the AWE. IL-1.ra/beta ratio achieved the highest predictive accuracy [area under the curve (AUC), 0.96] for AWE, followed by IL-1.ra (AUC, 0.90), IL-1β (AUC, 0.88) and TNF-α (AUC, 0.85). As compared with the UIAs without AWE, the AWE UIAs were manifested as a severer wall remodeling, with higher relative levels of pyroptosis-related proteins, CD68 and MMP2. The serum IL-1β, IL-1.ra and IL-1.ra/beta ratio had a positive correlation with the relative levels of pyroptosis-related proteins, CD68 and MMP2 in UIA tissues.

Conclusion: The serum IL-1β and IL-1.ra were correlated with the AWE. More pyroptosis-related proteins were identified in UIAs with AWE. The serum IL-1β and IL-1.ra were correlated with the pyroptosis-related proteins in aneurysm tissues.

Keywords: IL-1; aneurysm wall enhancement; pyroptosis; serum cytokines; unruptured intracranial aneurysm.