Circulating levels of interleukin 6 soluble receptor and its natural antagonist, sgp130, and the risk of myocardial infarction

Velásquez, Ilais Moreno; Golabkesh, Zahra; Källberg, Henrik; Leander, Karin; Fairé, Ulf dé; Gigante, Bruna

doi:10.1016/j.atherosclerosis.2015.04.014

Cited by 36 publications

(21 citation statements)

References 38 publications

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“…sgp130 has been proposed to have pleiotropic properties and may have anti‐inflammatory effects by serving as an inhibitor of the sIL‐6R/IL‐6 complex . In a recent study, high levels of sgp130 were suggested to be beneficial and protective in myocardial infarction, which differs somewhat from our results. The diverging results may be attributed to the different time points of blood sampling.…”

Section: Discussioncontrasting

confidence: 99%

“…The present results on patients with relatively small‐to‐moderate infarct size judged by troponin levels indicate that other important mechanisms are involved in the risk of new cardiovascular events during the first years after an myocardial infarction. Our results can be discussed in line with the recent report of Moreno Velasquez et al., showing that high levels of sIL‐6R, although measured in a stable phase after an STEMI, were related to the occurrence of future myocardial infarction. It has also been reported that high levels of sIL‐6R were associated with reduced myocardial reperfusion in STEMI patients undergoing acute PCI, indicating a role of sIL‐6R and inflammation in ischemia‐reperfusion injury.…”

Section: Discussionsupporting

confidence: 92%

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Circulating Levels of IL‐6 Receptor and gp130 and Long‐Term Clinical Outcomes in ST‐Elevation Myocardial Infarction

Ritschel

Seljeflot

Arnesen

et al. 2016

JAHA

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BackgroundReports on soluble interleukin‐6 (IL‐6) receptor (sIL‐6R) and glycoprotein 130 (sgp130) in ST‐elevation myocardial infarction (STEMI) are few and include a small number of patients. The aim of this study was to investigate the possible association between levels of these biomarkers in the acute phase of STEMI and future cardiovascular events.Methods and ResultsCirculating IL‐6, sgp130, sIL‐6R, and C‐reactive protein (CRP) were measured in 989 STEMI patients during 2007–2011, and cardiovascular events were recorded during follow‐up. The primary endpoint was composite of all‐cause mortality, myocardial infarction, stroke, unscheduled revascularization, or rehospitalization for heart failure. Cox regression models were used to estimate hazard ratios (HRs) for cardiovascular events in relation to biomarker levels. Median levels of sIL‐6R, sgp130, IL‐6, and CRP measured 24 hours (median) after symptom onset were 39.2 ng/mL, 240 ng/mL, 18.8 pg/mL, and 13.7 mg/L, respectively. During a median follow‐up time of 4.6 years, 200 patients (20.2%) experienced a primary endpoint, and 82 patients (8.3%) died. Patients with sIL‐6R levels in the upper quartile (>47.7 ng/mL) had significantly higher risk of future adverse events (primary endpoint) and mortality compared to patients with lower levels (adjusted HR, 1.54 [1.08, 2.21]; P=0.02 and 1.81 [1.04, 3.18]; P=0.04, respectively). Neither IL‐6 nor sgp130 levels were related to future events, but patients with CRP levels in the upper quartile (>31.5 mg/L) had higher risk of death.ConclusionHigh levels of sIL‐6R were associated with future cardiovascular events and mortality in STEMI patients, suggesting an important role of the IL‐6 signaling system.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 92%

Circulating Levels of IL‐6 Receptor and gp130 and Long‐Term Clinical Outcomes in ST‐Elevation Myocardial Infarction

Ritschel

Seljeflot

Arnesen

et al. 2016

JAHA

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“…Unlike sIL-6R, sgp130 is predominantly generated by alternative splicing rather than proteolysis (45). Since sgp130 can interact with the IL-6/sIL-6R complex, it acts as a specific inhibitor of IL-6 trans-signaling pathway (46, 47), whereas it does not affect mbIL-6R-mediated classic signaling. Notably, sgp130 is specific for the IL-6/sIL-6R complex due to signaling of other IL-6 family cytokines like LIF and OSM were blocked at 100–1,000-folds higher concentrations and CNTF and IL-27 signaling were not affected at all (46, 48, 49).…”

Section: Classic and Trans-signaling Pathway Of Il-6mentioning

confidence: 99%

Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update

2017

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Interleukin-6 (IL-6) is a pleiotropic cytokine that not only regulates the immune and inflammatory response but also affects hematopoiesis, metabolism, and organ development. IL-6 can simultaneously elicit distinct or even contradictory physiopathological processes, which is likely discriminated by the cascades of signaling pathway, termed classic and trans-signaling. Besides playing several important physiological roles, dysregulated IL-6 has been demonstrated to underlie a number of autoimmune and inflammatory diseases, metabolic abnormalities, and malignancies. This review provides an overview of basic concept of IL-6 signaling pathway as well as the interplay between IL-6 and renal-resident cells, including podocytes, mesangial cells, endothelial cells, and tubular epithelial cells. Additionally, we summarize the roles of IL-6 in several renal diseases, such as IgA nephropathy, lupus nephritis, diabetic nephropathy, acute kidney injury, and chronic kidney disease.

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“…On the other hand, the presence of soluble glycoprotein 130 (sgp130), which inhibits IL-6 trans-signalling [14], may modify the association between elevated interleukin 6 soluble receptor (sIL6R) levels and myocardial infarction [15]. The chemokine CXCL12 (SDF-1α) controls the functions of bone marrow-derived stem cell functions and neurogenesis and there are decreased level of CXCL12 in early Alzheimer’s disease [16].…”

Section: Introductionmentioning

confidence: 99%

Effects of Horticultural Therapy on Asian Older Adults: A Randomized Controlled Trial

Kst

Sia

Mkw

et al. 2018

IJERPH

112

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The effect of horticultural therapy (HT) on immune and endocrine biomarkers remains largely unknown. We designed a waitlist-control randomized controlled trial to investigate the effectiveness of HT in improving mental well-being and modulating biomarker levels. A total of 59 older adults was recruited, with 29 randomly assigned to the HT intervention and 30 to the waitlist control group. The participants attended weekly intervention sessions for the first 3 months and monthly sessions for the subsequent 3 months. Biological and psychosocial data were collected. Biomarkers included IL-1β, IL-6, sgp-130, CXCL12/SDF-1α, CCL-5/RANTES, BDNF (brain-derived neurotrophic factor), hs-CRP, cortisol and DHEA (dehydroepiandrosterone). Psychosocial measures examined cognitive functions, depression, anxiety, psychological well-being, social connectedness and satisfaction with life. A significant reduction in plasma IL-6 level (p = 0.02) was observed in the HT intervention group. For the waitlist control group, significant reductions in plasma CXCL12 (SDF-1α) (p = 0.003), CXCL5 (RANTES) (p = 0.05) and BDNF (p = 0.003) were observed. A significant improvement in social connectedness was also observed in the HT group (p = 0.01). Conclusion: HT, in reducing plasma IL-6, may prevent inflammatory disorders and through maintaining plasma CXCL12 (SDF-1α), may maintain hematopoietic support to the brain. HT may be applied in communal gardening to enhance the well-being of older adults.

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Circulating levels of interleukin 6 soluble receptor and its natural antagonist, sgp130, and the risk of myocardial infarction

Cited by 36 publications

References 38 publications

Circulating Levels of IL‐6 Receptor and gp130 and Long‐Term Clinical Outcomes in ST‐Elevation Myocardial Infarction

Circulating Levels of IL‐6 Receptor and gp130 and Long‐Term Clinical Outcomes in ST‐Elevation Myocardial Infarction

Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update

Effects of Horticultural Therapy on Asian Older Adults: A Randomized Controlled Trial

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