Serum ST2 as a potential prognostic biomarker for traumatic brain injury

Du, Qin; Weng, Jianfeng; Luo, Lifeng; Cen, Meng; Yu, Wenhua; Zheng, Yongke; Hu, Wei; Pan, Jianwei; Dong, Xiao-Qiao

doi:10.1016/j.cca.2018.09.035

Cited by 23 publications

(16 citation statements)

References 67 publications

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“…sST2 is abundantly expressed in blood in healthy individuals, with increased levels detected in a variety of conditions. Previous studies have shown that levels of circulating sST2 are markedly increased in trauma patients (Brunner et al 2004;Du et al 2018;Xu et al 2017). IL-33, on the other hand, appears to be present in very low or undetectable levels in plasma or serum.…”

Section: Introductionmentioning

confidence: 90%

Rapid systemic surge of IL-33 after severe human trauma: a prospective observational study

Sundnes

Ottestad

Schjalm

et al. 2021

Mol Med

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Background Alarmins are considered proximal mediators of the immune response after tissue injury. Understanding their biology could pave the way for development of new therapeutic targets and biomarkers in human disease, including multiple trauma. In this study we explored high-resolution concentration kinetics of the alarmin interleukin-33 (IL-33) early after human trauma. Methods Plasma samples were serially collected from 136 trauma patients immediately after hospital admission, 2, 4, 6, and 8 h thereafter, and every morning in the ICU. Levels of IL-33 and its decoy receptor sST2 were measured by immunoassays. Results We observed a rapid and transient surge of IL-33 in a subset of critically injured patients. These patients had more widespread tissue injuries and a greater degree of early coagulopathy. IL-33 half-life (t1/2) was 1.4 h (95% CI 1.2–1.6). sST2 displayed a distinctly different pattern with low initial levels but massive increase at later time points. Conclusions We describe for the first time early high-resolution IL-33 concentration kinetics in individual patients after trauma and correlate systemic IL-33 release to clinical data. These findings provide insight into a potentially important axis of danger signaling in humans.

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Section: Introductionmentioning

confidence: 90%

Rapid systemic surge of IL-33 after severe human trauma: a prospective observational study

Sundnes

Ottestad

Schjalm

et al. 2021

Mol Med

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“…IL-33 has been reported to be increased in microdialysate samples of patients with TBI (11). Serum sST2 levels are also elevated in TBI patients, and the increased concentrations are positively related to inflammation, severity and prognosis (55), which indicates that sST2 is a potential prognostic biomarker for TBI. In mice, IL-33 is released immediately from damaged oligodendrocytes and astrocytes in injured CNS tissue during TBI induced by controlled cortical impact (CCI) and experimental SCI (4,11,13,56).…”

Section: Il-33 In Traumamentioning

confidence: 98%

Therapeutic Opportunities of Interleukin-33 in the Central Nervous System

et al. 2021

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Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is involved in various diseases. IL-33 exerts its effects via its heterodimeric receptor complex, which comprises suppression of tumorigenicity 2 (ST2) and the IL-1 receptor accessory protein (IL-1RAP). Increasing evidence has demonstrated that IL-33/ST2 signaling plays diverse but crucial roles in the homeostasis of the central nervous system (CNS) and the pathogenesis of CNS diseases, including neurodegenerative diseases, cerebrovascular diseases, infection, trauma, and ischemic stroke. In the current review, we focus on the functional roles and cellular signaling mechanisms of IL-33 in the CNS and evaluate the potential for diagnostic and therapeutic applications.

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“…Moreover, IL-33 has been associated with Alzheimer's disease, multiple sclerosis, schizophrenia, CNS injury, CNS parasitic infection, and glioma [14,[19][20][21]. Previous studies have shown that soluble ST2 (sST2) levels are significantly associated with pro-inflammatory responses, as well as severity and prognosis of disease, in traumatic brain injury [22]. Elevated serum sST2 levels have been detected in acute ischemic stroke [23].…”

Section: Effects Of Il-33 On the Central Nervous Systemmentioning

confidence: 99%

The Role of Pro-Inflammatory and Regulatory Signaling by IL-33 in the Brain and Liver: A Focused Systematic Review of Mouse and Human Data and Risk of Bias Assessment of the Literature

Zharichenko

Njoku

2020

IJMS

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Interleukin (IL)-33 is a member of the IL-1 family of proteins that have multiple roles in organ-specific inflammation. Many studies suggest diagnostic and therapeutic implications of this cytokine. Many studies have reported pro-inflammatory roles for IL-33 in innate immune responses involving the heart and lung. Recent studies also describe pro-inflammatory and regulatory roles for IL-33 in the pathogenesis of brain and liver disorders in addition to regulatory roles for this cytokine in the heart and lung. In this focused systematic review, we will review the literature regarding pro-inflammatory and regulatory effects of IL-33 in the brain and liver. We will also assess the potential risk of bias in the published literature in order to uncover gaps in the knowledge that will be useful for the scientific community. We utilized guidelines set by preferred reporting items for systemic reviews and meta-analyses. The electronic database was PubMed. Eligibility criteria included organ-specific inflammation in mice and humans, organ-specific inflammation in the central nervous and hepatic systems, and IL-33. Outcomes were pro-inflammatory or regulatory effects of IL-33. Risk of bias in individual studies and across studies was addressed by adapting the Cochrane Rob 2.0 tool. We discovered that a source of bias across the studies was a lack of randomization in human studies. Additionally, because the majority of studies were performed in mice, this could be perceived as a potential risk of bias. Regarding the central nervous system, roles for IL-33 in the development and maturation of neuronal circuits were reported; however, exact mechanisms by which this occurred were not elucidated. IL-33 was produced by astrocytes and endothelial cells while IL-33 receptors were expressed by microglia and astrocytes, demonstrating that these cells are first responders for IL-33; however, in the CNS, IL-33 seems to induce Th1 cytokines such as IL-1β and TNF-α chemokines such as RANTES, MCP-1, MIP-1α, and IP-10, as well as nitric oxide. In the liver, similar risks of bias were determined because of the lack of randomized controlled trials in humans and because the majority of studies were performed in mice. Interestingly, the strain of mouse utilized in the study seemed to affect the role of IL-33 in liver inflammation. Lastly, similar to the brain, IL-33 appeared to have ST2-independent regulatory functions in the liver. Our results reveal plausible gaps in what is known regarding IL-33 in the pathogenesis of brain and liver disorders. We highlight key studies in the lung and heart as examples of advancements that likely occurred because of countless basic and translational studies in this area. More research is needed in these areas in order to assess the diagnostic or therapeutic potential of IL-33 in these disorders.

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Serum ST2 as a potential prognostic biomarker for traumatic brain injury

Cited by 23 publications

References 67 publications

Rapid systemic surge of IL-33 after severe human trauma: a prospective observational study

Rapid systemic surge of IL-33 after severe human trauma: a prospective observational study

Therapeutic Opportunities of Interleukin-33 in the Central Nervous System

The Role of Pro-Inflammatory and Regulatory Signaling by IL-33 in the Brain and Liver: A Focused Systematic Review of Mouse and Human Data and Risk of Bias Assessment of the Literature

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