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

Abstract

Background and PurposeAneurysm 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.MethodsUIA 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.ResultsThis 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.ConclusionThe 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.

Circular RNA hsa_circ_0007990 as a blood biomarker for unruptured intracranial aneurysm with aneurysm wall enhancement

“…AWE on HR-VWI has been used as an imaging marker for vessel wall inflammation and aneurysm instability in patients with UIA. Recent studies showed the association of inflammatory blood biomarkers with AWE on HR-VWI in UIA patients (9)(10)(11)(12)(13). The plasma concentration of anti-inflammatory cytokine interleukin (IL)-10 in the aneurysm sac decreased in UIA with AWE (10).…”

“…There was histological inflammation infiltration in aneurysm tissues with AWE. The serum IL-1β, IL-1RA, and IL-1RA/IL-1β ratio were associated with the inflammation-related proteins in aneurysm tissues ( 13 ). These results suggested that systematic inflammatory cytokines in the peripheral blood correlated with inflammatory factors in aneurysm tissues with AWE on HR-VWI, which may be a potential biomarker for aneurysm instability in UIA.…”

“…Inflammation plays a vital role in the development and progression of intracranial aneurysms (IA), which can be reflected by aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI) (3)(4)(5)(6)(7)(8). Recent studies suggest the association of inflammatory blood biomarkers in the aneurysm sac and peripheral blood with AWE on HR-VWI in patients with UIA (9)(10)(11)(12)(13).…”

miR-139-5p Suppresses Proliferation and Angiogenesis of Intracranial Aneurysm via FGB

“…Interleukin-1 (IL-1) has been reported to play an important role in the immune and inflammatory responses in cerebrovascular diseases [ 18 , 19 ]. IL-1 β is one of the 3 members of the IL-1 family, which was highly expressed in intracranial aneurysm samples [ 20 ]. Previous studies showed the changes in TNF- α are related to human cerebral aneurysms.…”

Potential application of peripheral blood biomarkers in intracranial aneurysms

“…Liu et al ( 21 ) prospectively investigated the correlation between imaging, cytokines, and histological samples of patients with UIA. They demonstrated that aneurysm wall enhancement was associated with pyroptosis in UIA tissues and pyroptosis-related serum cytokines such as the inflammatory cytokine IL-1β and anti-inflammatory cytokine IL-1 receptor antagonist (IL-1.ra).…”