Circadian variations of interleukin 6 in coronary circulations of patients with myocardial infarction

Bonda, Tomasz A.; Kamiński, Karol; Kożuch, Marcin; Kozieradzka, Anna; Wojtkowska, Izabela; Dobrzycki, Sławomir; Kralisz, Paweł; Nowak, Konrad; Prokopczuk, Przemysław; Musiał, Włodzimierz J.

doi:10.1016/j.cyto.2010.01.007

“…Whereas genetic expression of the markers related to the NLRP3 inflammasome, as well as IL-6R, showed a positive association to peak troponin T, mRNA encoding gp130 in thrombi, and IL-6 in circulating leukocytes associated inversely with peak troponin T. This might be explained by the complexity of the IL-6 signaling system, with classic signaling, trans-signaling, soluble form of receptors, and maybe also feedback mechanisms. Circadian cycles of levels of IL-6 in STEMI-patients have been reported [ 33 ]. This can affect our results, as all patients in the study were included in daytime.…”

Section: Discussionmentioning

confidence: 99%

The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI

Nordeng

¹

,

Schandiz

²

,

Solheim

³

et al. 2021

Mediators of Inflammation

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Background. The Nod-Like-Receptor-Protein-3 (NLRP3) inflammasome and the Interleukin-6 (IL-6) pathways are central mechanisms of the inflammatory response in myocardial reperfusion injury. Expanding our knowledge about the inflammasome signaling axis is important to improve treatment options. In a cross-sectional study, we aimed to study presence, localization, and genetic expression of inflammasome- and IL-6- signaling-related proteins in coronary thrombi and circulating leukocytes from ST-elevation myocardial infarction (STEMI) patients, with relation to myocardial injury and time from symptoms to PCI. Methods. Intracoronary thrombi were aspirated from 33 STEMI patients. Blood samples were drawn. mRNA of Toll-Like-Receptor-4 (TLR4), NLRP3, caspase 1, Interleukin-1β (IL1-β), Interleukin-18 (IL-18), IL-6, IL-6-receptor (IL-6R), and glycoprotein 130 (gp130) were isolated from thrombi and circulating leukocytes and relatively quantified by RT-PCR. A part of each thrombus was embedded in paraffin for histology and immunohistochemistry analyses. Results. Genes encoding the 8 markers were present in 76-100% of thrombi. Expression of TLR4 in thrombi significantly correlated to troponin T ( r = 0.455 , p = 0.013 ), as did NLRP3 ( r = 0.468 , p = 0.024 ). Troponin T correlated with expression in circulating leukocytes of TLR4 ( r = 0.438 , p = 0.011 ), NLRP3 ( r = 0.420 , p = 0.0149 ), and IL-1β ( r = 0.394 , p = 0.023 ). IL-6R expression in thrombi correlated significantly to troponin T ( r = 0.434 , p = 0.019 ), whereas gp130 was inversely correlated ( r = − 0.398 , p = 0.050 ). IL-6 in circulating leukocytes correlated inversely to troponin T ( r = − 0.421 , p = 0.015 ). There were no significant correlations between genes expressed in thrombi and time from symptom to PCI. Conclusions. The inflammasome signaling pathway was actively regulated in coronary thrombi and in circulating leukocytes from patients with STEMI, in association with myocardial damage measured by troponin T. This supports the strategy of medically targeting this pathway in treating myocardial infarction and contributes to sort out optimal timing and targets for anti-inflammatory treatment. The study is registered at clinicaltrials.gov with identification number NCT02746822.

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“…This complex IL-6 signaling physiology and balance in pro-and anti-inflammatory effects has been investigated in several studies concerning cardiac patients. Imbalances were found in patients with severe chronic heart failure [20], in the local and circadian inflammatory reaction in the coronary blood stream of the ischemic heart [21,22]. Moreover, a small study in 31 patients investigated the effects of cardiopulmonary bypass (CPB) on IL-6, sIL-6R, and sgp130 in patients undergoing coronary artery bypass graft [7].…”

Section: Introductionmentioning

confidence: 99%

Characteristics of Interleukin-6 Signaling in Elective Cardiac Surgery—A Prospective Cohort Study

Puchinger

¹

,

Ryz

²

,

Nixdorf

³

et al. 2022

JCM

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Interleukin-6 (IL-6) can cause pro- and anti-inflammatory effects via different signaling pathways. This prospective study investigated the perioperative kinetics of IL-6, soluble IL-6 receptor (sIL-6R), and soluble glycoprotein 130 (sgp130) in elective patients undergoing cardiopulmonary bypass (CPB). IL-6, sIL-6R, and sgp130 were measured simultaneously and consecutively at 19 timepoints until the 10th postoperative day (POD). The proportion of pro- and anti-inflammatory pathways were determined by calculating sIL-6R/IL-6 and sIL-6R/sgp130 ratios. We analyzed 93 patients. IL-6 increased during surgery with reaching a plateau two hours after CPB and peaking on POD 1 (188.5 pg mL−1 (IQR, 126.6; 309.2)). sIL-6R decreased at the beginning of the surgical procedure, reaching a nadir level on POD 2 (26,311 pg mL−1 (IQR, 22,222; 33,606)). sgp130 dropped immediately after CPB initiation (0.13 ng mL−1 (IQR, 0.12; 0.15)), followed by a continuous recovery until POD10. The sIL-6R/IL-6 ratio decreased substantially at the beginning of the procedure, reaching a nadir on POD 1 (149.7 (IQR, 82.4; 237.4)), while the sIL-6R/sgp130 ratio increased simultaneously until 6 h post CPB (0.219 (IQR 0.18; 0.27)). In conclusion, IL-6 exhibited high inter-individual variability reflecting an inhomogeneous inflammatory response. Pro-inflammatory effects and overwhelming inflammation were rare and predominantly anti-inflammatory effects were found.

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“…IL6 is synthesized by several cell types such as hepatic broblasts, macrophages, and monocytes as well as fat cells, vasculature and myocardial cells [19]. A previous study suggests that the important secretion of IL-6 by adipose cells could explain CAD occurrence [20]. It has been shown that in large populations, IL6 compared to other in ammatory markers such as hsCRP and LpPLA2, appears to be the most predictive marker of clinical manifestations even at early stages.…”

Section: Discussionmentioning

confidence: 99%

Relationship between serum interleukin-6 levels and severity of coronary artery disease undergoing percutaneous coronary intervention

Bouzidi

¹

,

Gamra

²

2023

Preprint

0

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Background: Cytokines play a potential role in atherosclerosis pathogenesis and progression. We investigated the association of interleukin-6 (IL-6) with the angiographic severity of coronary artery disease (CAD). Methods: 310 angiografically diagnosed CAD patients and 210 controls were enrolled in this study. CAD patients were stratified according to IL-6 cut-off value into high levels IL-6 group (≥ 9.5 pg/mL) and low levels IL-6 group (< 9.5 pg/mL). The severity of CAD was assessed according to Gensini score (GS), artery stenosis degree and the number of vessels involved. The mean age was 60.3 ± 11.0 years. Results:The level of IL-6 in patients was increased compared to controls and ranged from 1.5 to 3640.0 pg/mL. High levels of IL-6 were significantly associated with high levels of GS (>40) but not with stenosis degree and vessel score. GS levels were significantly more elevated in patients with high levels of IL-6 group than in low IL6 levels patients (60.6 ± 39.5 vs 46.7 ± 37.2; p = 0.027). The analysis of the ROC curve performed in myocardial infarction patients showed that IL-6 (AUC: 0.941 (CI 95% 0.886, 0.997; p<0.001) could be a powerful predictor marker in evaluating the infarct size after myocardial infarction when compared to myonecrosis biomarkers. Conclusions: IL-6 levels were associated with the severity of CAD assessed by the GS. Based on the highest levels of IL-6 measured in patients with STEMI, our study strongly suggests that IL-6 could be a powerful marker in evaluating the myocardial necrosis. ClinicalTrials.gov Number: NCT03075566 (09/03/2017)

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Circadian variations of interleukin 6 in coronary circulations of patients with myocardial infarction

Cited by 12 publications

References 26 publications

The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI

The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI

Characteristics of Interleukin-6 Signaling in Elective Cardiac Surgery—A Prospective Cohort Study

Relationship between serum interleukin-6 levels and severity of coronary artery disease undergoing percutaneous coronary intervention

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