Prospective assessment of cytokine IL-15 activity in patients with refractory atrial fibrillation episodes

Borowiec, Anna; Kontny, Ewa; Smolis−Bąk, Edyta; Kowalik, Ilona; Majos, E; Zalucka, L; Plazinski, K.; Maśliński, Włodzimierz; Szwed, Hanna; Dąbrowski, Rafał

doi:10.1016/j.cyto.2015.04.002

Cited by 11 publications

(5 citation statements)

References 31 publications

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“…Several pro-inflammatory cytokines (IL-6, IFN-γ and IL-15) were higher in the cardiac events group. This is in line with prior studies showing elevated IL-6 and IL-15 in patients with atrial fibrillation [ 27 , 28 ]. However, the differences in the level of different cytokines were not significant enough to be used for clinical purpose.…”

Section: Discussionsupporting

confidence: 93%

Cardiac and inflammatory biomarker differences in adverse cardiac events after chimeric antigen receptor T-Cell therapy: an exploratory study

et al. 2023

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Background Chimeric antigen receptor T- Cell (CAR-T) immunotherapy has been a breakthrough treatment for various hematological malignancies. However, cardiotoxicities such as new-onset heart failure, arrhythmia, acute coronary syndrome and cardiovascular death occur in 10–15% of patients treated with CAR-T. This study aims to investigate the changes in cardiac and inflammatory biomarkers in CAR-T therapy to determine the role of pro-inflammatory cytokines. Methods In this observational study, ninety consecutive patients treated with CAR-T underwent baseline cardiac investigation with electrocardiogram (ECG), transthoracic echocardiogram (TTE), troponin-I, and B-type natriuretic peptide (BNP). Follow-up ECG, troponin-I and BNP were obtained five days post- CAR-T. In a subset of patients (N = 53), serum inflammatory cytokines interleukin (IL)-2, IL-6, IL-15, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and angiopoietin 1 & 2 were tested serially, including baseline and daily during hospitalization. Adverse cardiac events were defined as new-onset cardiomyopathy/heart failure, acute coronary syndrome, arrhythmia and cardiovascular death. Results Eleven patients (12%) had adverse cardiac events (one with new-onset cardiomyopathy and ten with new-onset atrial fibrillation). Adverse cardiac events appear to have occurred among patients with advanced age (77 vs. 66 years; p = 0.002), higher baseline creatinine (0.9 vs. 0.7 mg/dL; 0.007) and higher left atrial volume index (23.9 vs. 16.9mL/m2; p = 0.042). Day 5 BNP levels (125 vs. 63pg/mL; p = 0.019), but not troponin-I, were higher in patients with adverse cardiac events, compared to those without. The maximum levels of IL-6 (3855.0 vs. 254.0 pg/mL; p = 0.021), IFN-γ (474.0 vs. 48.8pg/mL; p = 0.006) and IL-15 (70.2 vs. 39.2pg/mL; p = 0.026) were also higher in the adverse cardiac events group. However, cardiac and inflammatory biomarker levels were not associated with cardiac events. Patients who developed cardiac events did not exhibit worse survival compared to patients without cardiac events (Log-rank p = 0.200). Conclusion Adverse cardiac events, predominantly atrial fibrillation, occur commonly after CAR-T (12%). The changes in serial inflammatory cytokine after CAR-T in the setting of adverse cardiac events suggests pro-inflammation as a pathophysiology and require further investigation for their role in adverse cardiac events. Tweet brief handle CAR-T related Cardiotoxicity has elevated cardiac and inflammatory biomarkers. #CARTCell #CardioOnc #CardioImmunology.

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Section: Discussionsupporting

confidence: 93%

Cardiac and inflammatory biomarker differences in adverse cardiac events after chimeric antigen receptor T-Cell therapy: an exploratory study

et al. 2023

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“…Recent evidence indicates that activated macrophages secrete other cytokines such as TNF-a and IL-1b, which can be involved in AF onset through the modifications of Ca 2+ currents and subsequent arrhythmia [43]. Moreover, increased levels of IL-1b, IL-2, IL-8, IL-9, IL-10, IL-15, IL-17A, IL-17F, IL-21, IL-22, interferong, and transforming growth factor-b1 [44][45][46][47][48] were also associated with AF onset. All these studies support the idea that a general proinflammatory status rather than the increased level of a single inflammation marker is responsible for the occurrence of post-operative AF.…”

Section: Discussionmentioning

confidence: 99%

Increased C-reactive protein plasma levels are not involved in the onset of post-operative atrial fibrillation

Campo

Roldán

Verdejo

et al. 2017

Journal of Cardiology

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“…enhanced in patients with heart failure, atrial fibrillation and myocardial infarction (9)(10)(11). Pharmacological inhibition of drp1 prevents mitochondrial fission in TNF-α-treated cells (12).…”

Section: Tnf-α Induces Drp1-mediated Mitochondrial Fragmentation During Inflammatory Cardiomyocyte Injurymentioning

confidence: 99%

TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury

et al. 2018

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Dynamin-related peptide 1 (Drpl)-mediated mitochondrial fission is an important process associated with cardiac dysfunction under different pathological conditions. The aim of the present study was to investigate the expression of Drpl during inflammatory myocardial injury. Sprague‑Dawley rats were treated intraperitoneally with lipopolysaccharides (LPS). Furthermore, cultured H9C2 cardiomyocytes were treated with LPS, interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α). Total and mitochondrial proteins were isolated from the heart tissue of rats and from the H9C2 cardiomyocytes. Expression levels of Drp1 and RhoA were analyzed by western blotting. Mitochondrial morphology was determined using confocal laser microscopy. The levels of mitochondrial Drp1 and phosphorylated‑Drp1 (p‑Drp1) Ser616 were revealed to be increased in rats 6 h after injection with LPS (5, 10 or 20 mg/kg). Furthermore, treatment with LPS and IL‑6 did not demonstrate a significant effect on the expression of total and mitochondrial Drp1 in H9C2 cardiomyocytes in vitro; however, treatment with TNF‑α (20 ng/ml) significantly enhanced the levels of mitochondrial Drp1 and p‑Drp1 Ser616. Following TNF‑α treatment, the expression of Ras homolog gene family member A (RhoA) was also revealed to increase. Treatment with both Y‑27632 and fasudil, [Rho kinase (ROCK) inhibitors], was demonstrated to attenuate the otherwise TNF‑α‑induced increase in p‑Drp1 Ser616 and mitochondrial Drp1. In addition, it was revealed that Y‑27632 and fasudil may also attenuate the TNF‑α‑induced increase in mitochondrial fragmentation and cell viability. Therefore, the findings of the present study suggest that TNF‑α is the predominant inducer of Drp1 S616 phosphorylation during sepsis. The results of the present study also suggest that the RhoA/ROCK pathway may be involved in the phosphorylation and mitochondrial translocation of Drp1, which leads to mitochondrial fragmentation.

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Prospective assessment of cytokine IL-15 activity in patients with refractory atrial fibrillation episodes

Cited by 11 publications

References 31 publications

Cardiac and inflammatory biomarker differences in adverse cardiac events after chimeric antigen receptor T-Cell therapy: an exploratory study

Cardiac and inflammatory biomarker differences in adverse cardiac events after chimeric antigen receptor T-Cell therapy: an exploratory study

Increased C-reactive protein plasma levels are not involved in the onset of post-operative atrial fibrillation

TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury

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