interleukin-8 and ST-Elevation-Myocardial-Infarction

Tocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and their correlations with neutrophils, C-reactive protein (CRP), troponin T, MSI and infarct size.. STEMI patients were randomised to receive a single dose of 280 mg tocilizumab (n=101) or placebo (n=98) before percutaneous coronary intervention. Blood samples were collected before infusion of tocilizumab or placebo at baseline, during follow-up at 24-36, 72-168 hours, 3 and 6 months. 27 cytokines were analysed using a multiplex cytokine assay. Cardiac MRI was performed during hospitalisation and 6 months.. Repeated measures analysis of variance showed significant (p<0.001) between-group difference in changes for IL-6, IL-8 and IL-1ra due to an increase in the tocilizumab group during hospitalisation. IL-6 and IL-8 correlated to neutrophils in the placebo group (r=0.73, 0.68, respectively), which was attenuated in the tocilizumab group (r=0.28, 0.27, respectively). A similar pattern was seen for MSI and IL-6 and IL-8 in the placebo group (r=-0.29, -0.25, respectively) in patients presenting ≤3 hours from symptom onset, which was attenuated in the tocilizumab group (r=-0.09,-0.14, respectively).. Tocilizumab increases IL-6, IL-8 and IL-1ra in STEMI. IL-6 and IL-8 show correlations to neutrophils/CRP and markers of cardiac injury in the placebo group that was attenuated in the tocilizumab group. This may suggest a beneficial effect of tocilizumab on the ischaemia-reperfusion injury in STEMI patients.. NCT03004703.

Topics: C-Reactive Protein; Cytokines; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Interleukin-8; Receptors, Interleukin-6; ST Elevation Myocardial Infarction

The role of neutrophil extracellular traps (NETs) in acute heart failure is unknown. We recently showed that interleukin 8, a putative NETs stimulator, was associated with myocardial recovery in acute heart failure complicating ST-elevation myocardial infarction (STEMI). In this exploratory post-hoc study, we aimed to investigate the role of NETs components in relation to myocardial function and interleukin 8 in STEMI patients with symptomatic acute heart failure.. In 61 STEMI patients developing acute heart failure within 48 hours of successful revascularization, wall motion score index (WMSI), global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) were assessed by echocardiography at baseline and on day 5. Blood drawn at baseline and days 1, 2 and 5 was used to quantify double-stranded DNA (dsDNA), myeloperoxidase-DNA complexes (MPO-DNA) and citrullinated histone 3 (CitH3). The area under the curve (AUC) of each NETs marker and interleukin 8 was approximated for the first 5 days.. dsDNAAUC and MPO-DNAAUC correlated significantly with change in WMSI from baseline to day 5 (rs = 0.28 for both, p≤0.05), whereas NETs AUCs did not correlate with changes in GLS and LVEF. dsDNAAUC was significantly correlated with interleukin 8AUC (r = 0.40, p = 0.003). However, mixed model regression could not identify a significant effect of the NETs components on myocardial function parameters.. In this cohort with acute heart failure complicating STEMI, NETs components were partly correlated with myocardial function and interleukin 8 levels, yet no causal relationship between NETs components and myocardial recovery could be established.. ClinicalTrials.gov, identifier: NCT00324766.

Topics: Adult; Aged; Aged, 80 and over; DNA; Echocardiography; Extracellular Traps; Female; Heart Failure; Histones; Humans; Interleukin-8; Male; Middle Aged; Myocardium; Peroxidase; Recovery of Function; ST Elevation Myocardial Infarction

Little is known about the role of interleukin (IL)-8 in patients with acute ST-segment elevation myocardial infarction (STEMI).. The aims of this study were to evaluate, in STEMI patients, the temporal profile of IL-8 and possible associations with left ventricular (LV) function and remodeling, infarct size, microvascular obstruction, myocardial salvage, and future clinical events.. A total of 258 patients with STEMI were included. Blood samples were drawn before and immediately after percutaneous coronary intervention (PCI), at day 1, and after 4 months. Cardiac magnetic resonance imaging was performed in the acute phase and after 4 months. Clinical events were registered during 12 months' follow-up and all-cause mortality after median 70 months' follow-up.. Patients with IL-8 levels greater than the median measured both immediately after PCI and at day 1 had larger final infarct size, lower LV ejection fraction, larger increase in LV end-diastolic volume, and higher frequency of microvascular obstruction. After multivariate adjustment, high IL-8 levels at day 1 were associated with an increased risk of developing a large MI and having reduced LV ejection fraction at 4 months, also after adjustment for peak troponin value. Patients with IL-8 levels in the highest quartile measured at all sampling points were more likely to have a clinical event during the first 12 months after the MI and had lower overall survival during long-term follow-up.. High levels of circulating IL-8 were associated with large infarct size, impaired recovery of LV function, and adverse clinical outcome in patients with STEMI, suggesting IL-8 as a future therapeutic target based on its important role in post-infarction inflammation.

Topics: Aged; Female; Humans; Interleukin-8; Male; Middle Aged; Myocardium; Prospective Studies; ST Elevation Myocardial Infarction; Stroke Volume; Ventricular Remodeling

The aim of this study was to investigate the association between inflammatory markers and 28-day mortality in patients with ST-elevation myocardial infarction (STEMI).. In 398 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 protein biomarkers were measured in admission arterial blood samples using the OLINK inflammatory panel. In multivariable-adjusted logistic regression models, the association between each marker and 28-day mortality was investigated. The values of the biomarkers most significantly associated with mortality were standardized and summarized to obtain a prediction score for 28-day mortality. The predictive ability of this biomarker score was compared to the established GRACE score using ROC analysis. Finally, a combined total score was generated by adding the standardized biomarker score to the standardized GRACE score.. The markers IL-6, IL-8, IL-10, FGF-21, FGF-23, ST1A1, MCP-1, 4E-BP1, and CST5 were most significantly associated with 28-day mortality, each with FDR-adjusted (false discovery rate adjusted) p-values of < 0.01 in the multivariable logistic regression model. In a ROC analysis, the biomarker score and the GRACE score showed comparable predictive ability for 28-day mortality (biomarker score AUC: 0.7859 [CI: 0.6735-0.89], GRACE score AUC: 0.7961 [CI: 0.6965-0.8802]). By combining the biomarker score and the Grace score, the predictive ability improved with an AUC of 0.8305 [CI: 0.7269-0.9187]. A continuous Net Reclassification Improvement (cNRI) of 0.566 (CI: 0.192-0.94, p-value: 0.003) and an Integrated Discrimination Improvement (IDI) of 0.083 ((CI: 0.016-0.149, p-value: 0.015) confirmed the superiority of the combined score over the GARCE score.. Inflammatory biomarkers may play a significant role in the pathophysiology of acute myocardial infarction (AMI) and AMI-related mortality and might be a promising starting point for personalized medicine, which aims to provide each patient with tailored therapy.

Topics: Biomarkers; Blood Proteins; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Myocardial Infarction; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction

Inflammatory cytokines modulate atherogenesis and plaque rupture to involve in ST-segment elevation myocardial infarction (STEMI) progression. The present study determined eight inflammatory cytokine levels in 212 percutaneous coronary intervention (PCI)-treated STEMI patients, aiming to comprehensively investigate their potency in estimating major adverse cardiac event (MACE) risk.. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) of 212 PCI-treated STEMI patients and 30 angina pectoris patients were determined using enzyme-linked immunosorbent assay.. TNF-α (52.5 (43.9-62.6) pg/ml versus 46.4 (39.0-59.1) pg/ml, p = 0.031), IL-8 (61.6 (49.6-81.7) pg/ml versus 46.7 (32.5-63.1) pg/ml, p = 0.001), IL-17A (57.4 (45.7-77.3) pg/ml versus 43.2 (34.2-64.6) pg/ml, p = 0.001), and VCAM-1 (593.6 (503.4-811.4) ng/ml versus 493.8 (390.3-653.7) ng/ml, p = 0.004) levels were elevated in STEMI patients compared to angina pectoris patients, while IL-1β (p = 0.069), IL-6 (p = 0.110), IL-10 (p = 0.052), and ICAM-1 (p = 0.069) were of no difference. Moreover, both IL-17A high (vs. low) (p = 0.026) and VCAM-1 high (vs. low) (p = 0.012) were linked with increased cumulative MACE rate. The multivariable Cox's analysis exhibited that IL-17A high (vs. low) (p = 0.034) and VCAM-1 high (vs. low) (p = 0.014) were independently associated with increased cumulative MACE risk. Additionally, age, diabetes mellitus, C-reactive protein, multivessel disease, stent length, and stent type were also independent factors for cumulative MACE risk.. IL-17A and VCAM-1 high level independently correlate with elevated MACE risk in STEMI patients, implying its potency in identifying patients with poor prognoses.

Topics: Angina Pectoris; Cytokines; Humans; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-17; Interleukin-6; Interleukin-8; Percutaneous Coronary Intervention; Prognosis; ST Elevation Myocardial Infarction; Treatment Outcome; Vascular Cell Adhesion Molecule-1

Topics: Goals; Humans; Inflammation; Interleukin-8; Myocardial Infarction; ST Elevation Myocardial Infarction