Early measurement of interleukin-10 predicts the absence of CT scan lesions in mild traumatic brain injury

Lagerstedt, Linnéa; Egea-Guerrero, Juan José; Rodríguez-Rodríguez, A.; Bustamante, Alejandro; Montaner, Joan; Rahal, Amir El; Andereggen, E; Rinaldi, Lara; Sarrafzadeh, Asita; Schaller, Karl; Sanchez, Jean‐Charles

doi:10.1371/journal.pone.0193278

Cited by 41 publications

(27 citation statements)

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“…The four proteins—S100B, GFAP, H-FABP and IL-10—have all previously been identified for their potential to differentiate CT-positive and CT-negative mTBI patients, confirming the results found here. [ 10 , 16 , 19 , 41 ] The proteins have been shown to be released from or leak out of different types of injured cells. Indeed, S100B and GFAP leak from injured astrocytes, H-FABP leaks from endothelial cells and neuron cell bodies, whereas Il-10 is expressed by monocytes and macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…A total of 13 proteins—H-FABP, the matrix metalloproteinases 1, 3 and 9 (MMP-1, MMP-3 and MMP-9 respectively), the vascular and intravascular cell adhesion molecules (VCAM and ICAM respectively), IL-10, the inflammatory proteins serum amyloid A (SAA) and C-reactive protein (CRP), the oxidative stress proteins glutathione S-transferase pi (GSTP), nucleoside diphosphate kinase A (NKDA) and peroxiredoxin 1 (PRDX1) and the parkinson disease protein 7 (PARK7/DJ-1)—were chosen. [ 10 , 16 , 23 , 32 – 37 ] These proteins were investigated for their individual performances as CT-scan triage biomarkers in mTBI patients with a GCS score of 15 and at least one clinical symptom. The best-performing proteins were then compared with the two most studied mTBI biomarkers: S100B and GFAP.…”

Section: Introductionmentioning

confidence: 99%

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Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury

et al. 2018

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Mild traumatic brain injury (mTBI) patients may have trauma-induced brain lesions detectable using CT scans. However, most patients will be CT-negative. There is thus a need for an additional tool to detect patients at risk. Single blood biomarkers, such as S100B and GFAP, have been widely studied in mTBI patients, but to date, none seems to perform well enough. In many different diseases, combining several biomarkers into panels has become increasingly interesting for diagnoses and to enhance classification performance. The present study evaluated 13 proteins individually—H-FABP, MMP-1, MMP-3, MMP-9, VCAM, ICAM, SAA, CRP, GSTP, NKDA, PRDX1, DJ-1 and IL-10—for their capacity to differentiate between patients with and without a brain lesion according to CT results. The best performing proteins were then compared and combined with the S100B and GFAP proteins into a CT-scan triage panel. Patients diagnosed with mTBI, with a Glasgow Coma Scale score of 15 and one additional clinical symptom were enrolled at three different European sites. A blood sample was collected at hospital admission, and a CT scan was performed. Patients were divided into two two-centre cohorts and further dichotomised into CT-positive and CT-negative groups for statistical analysis. Single markers and panels were evaluated using Cohort 1. Four proteins—H-FABP, IL-10, S100B and GFAP—showed significantly higher levels in CT-positive patients. The best-performing biomarker was H-FABP, with a specificity of 32% (95% CI 23–40) and sensitivity reaching 100%. The best-performing two-marker panel for Cohort 1, subsequently validated in Cohort 2, was a combination of H-FABP and GFAP, enhancing specificity to 46% (95% CI 36–55). When adding IL-10 to this panel, specificity reached 52% (95% CI 43–61) with 100% sensitivity. These results showed that proteins combined into panels could be used to efficiently classify CT-positive and CT-negative mTBI patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury

et al. 2018

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“…A biomarker especially for triage of patients with mTBI to guide diagnostic procedures is warranted; however, previous studies have demonstrated low specificity for inflammatory markers for predicting, for example, CT findings. 51 Thus, further studies are needed to investigate if the demonstrated inflammatory state is caused by neuroinflammation, and what are the clinical implications of prolonged inflammation with INFLAMMATION PERSISTS ONE YEAR AFTER MTBI outcome, such as post-concussion syndrome, and potential for manipulating it for improved outcome.…”

Section: Implications For Diagnosis Follow-up and Therapymentioning

confidence: 99%

Systemic Inflammation Persists the First Year after Mild Traumatic Brain Injury: Results from the Prospective Trondheim Mild Traumatic Brain Injury Study

Chaban

Clarke

Skandsen

et al. 2020

Journal of Neurotrauma

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Innate immune activation has been attributed a key role in traumatic brain injury (TBI) and successive morbidity. In mild TBI (mTBI), however, the extent and persistence of innate immune activation are unknown. We determined plasma cytokine level changes over 12 months after an mTBI in hospitalized and non-hospitalized patients compared with community controls; and examined their associations to injury-related and demographic variables at admission. Prospectively, 207 patients presenting to the emergency department (ED) or general practitioner with clinically confirmed mTBI and 82 matched community controls were included. Plasma samples were obtained at admission, after 2 weeks, 3 months, and 12 months. Cytokine levels were analysed with a 27-plex beads-based immunoassay. Brain magnetic resonance imaging (MRI) was performed on all participants. Twelve cytokines were reliably detected. Plasma levels of interferon gamma (IFN-c), interleukin 8 (IL-8), eotaxin, macrophage inflammatory protein-1-beta (MIP-1b), monocyte chemoattractant protein 1 (MCP-1), IL-17A, IL-9, tumor necrosis factor (TNF), and basic fibroblast growth factor (FGFbasic) were significantly increased at all time-points in patients compared with controls, whereas IFN-c-inducing protein 10 (IP-10), platelet-derived growth factor (PDGF), and IL-1ra were not. IL-17A and FGF-basic showed significant increases in patients from admission to follow-up at 3 months, and remained increased at 12 months compared with admission. Interestingly, MRI findings were negatively associated with four cytokines: eotaxin, MIP-1b, IL-9, and IP-10, whereas age was positively associated with nine cytokines: IL-8, eotaxin, MIP-1b, MCP-1, IL-17A, IL-9, TNF, FGFbasic, and IL-1ra. TNF was also increased in those with presence of other injuries. In conclusion, mTBI activated the innate immune system consistently and this is the first study to show that several inflammatory cytokines remain increased for up to 1 year post-injury.

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“…Clinically, after TBI different aspects of the inflammatory response are monitored, mainly by assessing markers of inflammation in different body fluids and sometimes tissue . By detecting cytokine profiles in blood, which is easily accessible, it is possible to both separate healthy individuals from patients with radiological visible injury , and predict outcome months after injury . However, detection of inflammatory markers in the cerebrospinal fluid (CSF) is often more specific for brain injuries as compared to blood.…”

Section: Human Pathology Of Ctementioning

confidence: 99%

Modelling human pathology of traumatic brain injury in animal models

et al. 2019

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Traumatic brain injury (TBI) is caused by a head impact with a force exceeding regular exposure from normal body movement which the brain normally can accommodate. People affected include, but are not restricted to, sport athletes in American football, ice hockey, boxing as well as military personnel. Both single and repetitive exposures may affect the brain acutely and can lead to chronic neurodegenerative changes including chronic traumatic encephalopathy associated with the development of dementia. The changes in the brain following TBI include neuroinflammation, white matter lesions, and axonal damage as well as hyperphosphorylation and aggregation of tau protein. Even though the human brain gross anatomy is different from rodents implicating different energy transfer upon impact, especially rotational forces, animal models of TBI are important tools to investigate the changes that occur upon TBI at molecular and cellular levels. Importantly, such models may help to increase the knowledge of how the pathologies develop, including the spreading of tau pathologies, and how to diagnose the severity of the TBI in the clinic. In addition, animal models are helpful in the development of novel biomarkers and can also be used to test potential disease‐modifying compounds in a preclinical setting.

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Early measurement of interleukin-10 predicts the absence of CT scan lesions in mild traumatic brain injury

Cited by 41 publications

References 44 publications

Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury

Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury

Systemic Inflammation Persists the First Year after Mild Traumatic Brain Injury: Results from the Prospective Trondheim Mild Traumatic Brain Injury Study

Modelling human pathology of traumatic brain injury in animal models

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