Expression of Cytokines and Chemokines as Predictors of Stroke Outcomes in Acute Ischemic Stroke

Martha, Sarah R; Cheng, Qiang; Fraser, Justin F.; Gong, Liyu; Collier, Lisa A.; Davis, Stephanie M.; Lukins, Douglas; Alhajeri, Abdulnasser; Grupke, Stephen; Pennypacker, Keith R.

doi:10.3389/fneur.2019.01391

Cited by 36 publications

(32 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, a number of studies have demonstrated that the blood levels of cytokines, chemokines, and growth factors, including C-reactive protein, TNF-α, IL-6 and IL-10, are associated with outcomes in AIS patients [14][15][16]. Although IL-2 is one of the most frequently studied cytokines in stroke patients, the conclusions are ambiguous and inconsistent with the results of experimental studies [17][18][19]. This might be due to the complexity of IL-2/IL-2R autocrine loops.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of plasma IL-2 and sIL-2Rα in patients with first-ever ischaemic stroke

Zhao

Huang

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

Background: An imbalance between circulating neuroprotective and neurotoxic T cell subsets leads to poor prognosis in acute ischaemic stroke (AIS). Preclinical studies have indicated that the soluble form of the interleukin-2 receptor α (sIL-2Rα)-IL-2 complex regulates T cell differentiation. However, the association between sIL-2Rα levels and AIS remains unclear. Methods: A total of 201 first-ever AIS patients within 24 h after stroke onset and 76 control subjects were recruited. The National Institutes of Health Stroke Scale (NIHSS) score and 3-month functional outcome (modified Rankin Scale [mRS] score) at admission were assessed. Plasma sIL-2Rα and IL-2 levels at admission were measured. Prognostic significance was identified by using univariate and multivariate logistic regression analyses. Results: Patients with poor functional outcomes at 3 months had significantly higher levels of sIL-2Rα and lower levels of IL-2 than patients with good outcomes. Moreover, sIL-2Rα levels showed a strong positive correlation with NIHSS and mRS scores (p < 0.0001), whereas IL-2 levels were negatively correlated with mRS scores (p < 0.01). Univariate analyses showed that higher sIL-2Rα and IL-2 levels were associated with an increased and reduced risk of unfavourable outcomes, respectively. After adjusting for confounding variables, the sIL-2Rα level remained independently associated with an increased risk of an unfavourable outcome, and adding sIL-2Rα levels to the conventional risk factor model significantly improved risk reclassification (net reclassification improvement 17.56%, p = 0.003; integrated discrimination improvement 5.78%, p = 0.0003). Conclusions: sIL-2Rα levels represent a novel, independent prognostic marker that can improve the currently used risk stratification of AIS patients. Our findings also highlight that elevated plasma sIL-2Rα and IL-2 levels manifested opposite correlations with functional outcome, underlining the importance of IL-2/IL-2R autocrine loops in AIS.

show abstract

Section: Discussionmentioning

confidence: 99%

Prognostic significance of plasma IL-2 and sIL-2Rα in patients with first-ever ischaemic stroke

Zhao

Huang

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…A dysregulated immune response, accompanied by an increased number of inflammatory cells, high TNF-α production and the activation of microglia cells has been shown to enhance neuroinflammation and exacerbate ischemic brain injury in patients with IS and a mouse model of cerebral ischemia ( 11 ). Inflammatory cytokines and chemokines have been used as predictors of stroke incidence and outcomes ( 12 , 13 ). Thus, the genetic variation of inflammatory cytokine genes has become a critical issue in research relating to the predictive risk factors of IS occurrence ( 14 , 15 ), as well as its severity and outcome ( 16 ), and this provides potential therapeutic options for the treatment of inflammatory diseases ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

Promoter polymorphism of TNF‑α (rs1800629) is associated with ischemic stroke susceptibility in a southern Thai population

et al. 2021

View full text Add to dashboard Cite

Stroke represents the leading cause of disability and mortality amongst the elderly worldwide. Multiple risk factors, including both genetic and non-genetic components, as well as their interactions, are proposed as etiological factors involved in the development of ischemic stroke (IS). Promoter polymorphisms of the IL-6-174G/C (rs1800795) and TNF-α-308G/A (rs1800629) genes have been considered as predictive risk factors of IS; however, these have not yet been evaluated in a Thai population. The aims of this study were to investigate the association of IL-6-174G/C and TNF-α-308G/A polymorphisms with IS. Genomic DNA from 200 patients with IS and 200 controls were genotyped for IL-6-174G/C and TNF-α-308G/A polymorphisms using TaqMan™ SNP genotyping and quantitative PCR-high resolution melting analysis, respectively. It was found that the TNF-α-308 A allele was significantly associated with an increased risk of IS development compared with the G allele [odds ratio (OR)=2.044; 95% CI=1.154-3.620; P=0.014]. Moreover, the IS risk was significantly higher in the presence of TNF-α-308 GA or AA genotypes compared with that in the presence of GG genotypes with a dominant inheritance (OR=1.971; 95% CI=1.080-3.599; P=0.027). However, there was no association between IL-6-174G/C and the risk of IS development. The interaction study demonstrated that IL-6-174 GG and TNF-α-308 GG genotypes enhanced IS susceptibility when combined with hypertension, hyperlipidemia and alcohol consumption. Hypertensive and hyperlipidemic subjects with the TNF-α-308 GA and AA genotypes were more likely to develop IS compared with those who did not have these two conditions and had the GG genotype. In a matched study design (1:1), the IL-6-174 GC genotype was associated with higher IL-6 levels in the control group. Collectively, the present results highlight the utility of the TNF-α-308G/A polymorphism as a predictive genetic risk factor for development of IS.

show abstract

“…Previously, we reported that genes related to a Th2 autoimmune response are elevated in intracranial blood from subjects during thrombectomy. 8 Changes in CCL23 support the gene data as CCL23 is induced by interleukin 4, a classic Th2 cytokine. 22 Proteins are drug targets for ischemic stroke.…”

Section: Discussionmentioning

confidence: 58%

Proteomic changes in intracranial blood during human ischemic stroke

Maglinger

Frank

McLouth

et al. 2020

J NeuroIntervent Surg

Self Cite

View full text Add to dashboard Cite

BackgroundSince 2015, mechanical thrombectomy has been the standard treatment for emergent large vessel occlusion ischemic stroke.ObjectiveTo investigate, using the previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683), how the protein expression of a patient’s intracranial blood during ischemic stroke compares with the protein expression of their systemic arterial blood in order to better understand and treat stroke.MethodsPlasma samples from 25 subjects underwent proteomic analysis, where intracranial protein expression was compared with systemic protein levels. Data including sex, comorbidities, infarct volume, and infarct time were included for each subject.ResultsA majority of important proteins had a lower expression in intracranial blood than in systemic arterial blood. Proteins with the most significant changes in expression were: endopeptidase at −0.26 (p<0.0001), phospholipid transfer protein (PLTP) at −0.26 (p=0.0005), uromodulin (UMOD) at −0.14 (p=0.002), ficolin-2 (FCN2) at −0.46 (p=0.005), C-C motif chemokine 19 (CCL19) at −0.51 (p<0.0001), C-C motif chemokine 20 (CCL20) at −0.40 (p<0.0001), fibroblast growth factor 21 at −0.37 (p=0.0002), and C-C motif chemokine (CCL23) at −0.43 (p=0.0003).ConclusionsEvaluation of proteomic changes in the intravascular space of a cerebral infarct in progress in human subjects suggested that changes in proteins such PLTP, fetuin-B (FETUB), and FCN2 may be involved in atherosclerotic changes, and chemokines such as CCL23 are known to play a role in the Th2 autoimmune response. These data provide a scientific springboard for identifying clinically relevant biomarkers for diagnosis/prognosis, and targets for much needed neuroprotective/neuroreparative pharmacotherapies.

show abstract

Expression of Cytokines and Chemokines as Predictors of Stroke Outcomes in Acute Ischemic Stroke

Abstract: Conclusions: Machine learning algorithms can be employed to develop prognostic predictive biomarkers for stroke outcomes in ischemic stroke patients, particularly in regard to identifying acute gene expression changes that occur during stroke.

Cited by 36 publications

References 69 publications

Prognostic significance of plasma IL-2 and sIL-2Rα in patients with first-ever ischaemic stroke

Prognostic significance of plasma IL-2 and sIL-2Rα in patients with first-ever ischaemic stroke

Promoter polymorphism of TNF‑α (rs1800629) is associated with ischemic stroke susceptibility in a southern Thai population

Proteomic changes in intracranial blood during human ischemic stroke

Contact Info

Product

Resources

About