The Role of Interleukin-6 Family Members in Cardiovascular Diseases

Feng, Yanqin; Ye, Di; Wang, Zhen; Pan, Heng; Lu, Xiyi; Wang, Menglong; Xu, Yao; Yu, Jin; Zhang, Jishou; Zhao, Mengmeng; Xu, Shou-Xi; Pan, Wei; Yin, Zheng; Ye, Jing; Wan, Jun

doi:10.3389/fcvm.2022.818890

Cited by 52 publications

(64 citation statements)

References 187 publications

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“…The pattern of cytokine secretion by helper and cytotoxic T cells is regulated by different modulatory signals including cytokines involved in the innate response [ 59 ]. IFNγ plays a critical role in the activation of cytotoxic T cells and NK cells [ 15 ]. IL-4, IL-5 and IL-9 show pivotal regulatory effects in B-lymphocyte differentiation and eosinophil activity [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…In general, soluble factors are a group of glycoproteins that play important roles in the development, cellular function and control of cells of the immune system and many other systems [ 12 , 13 , 14 ]. They are small secreted glycoproteins and proteolytically released from the cell surface, such as TNFα with autocrine, paracrine and endocrine roles usually produced upon the activation of cells of the immune system [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Many cytokines and soluble factors have been described, and several have been recognized as pivotal players in the immune system and human disease; in fact, many of them have been used as therapeutic tools [ 15 ]. Cytokines, unlike hormones, tend to be short-range protein mediators that carry out their activities at low concentrations, being able to perform pleiotropic, redundant and antagonistic functions.…”

Section: Introductionmentioning

confidence: 99%

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Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients

Monserrat

Gómez-Lahoz

Ortega

et al. 2022

IJMS

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SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system—IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII—for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFβ, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients

Monserrat

Gómez-Lahoz

Ortega

et al. 2022

IJMS

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“…The role of the kynurenine pathway in atherosclerotic disease has been extensively reviewed [113][114][115]. A state of low-grade inflammation in atherosclerosis is marked by increased levels of IL-6, an inducer of IDO [116]. Once more, research shows that decreased tryptophan and an increased kynurenine/tryptophan-ratio is associated with the severity of atherosclerosis [113] and thus indicating that increased IDO-activity is related to this state of low-grade inflammation.…”

Section: Atherosclerosismentioning

confidence: 99%

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

2022

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and therefore is its burden of disease as NALFD is a risk factor for cirrhosis and is associated with other metabolic conditions such as type II diabetes, obesity, dyslipidaemia and atherosclerosis. Linking these cardiometabolic diseases is a state of low-grade inflammation, with higher cytokines and c-reactive protein levels found in individuals with NAFLD, obesity and type II diabetes. A possible therapeutic target to decrease this state of low-grade inflammation is the metabolism of the essential amino-acid tryptophan. Its three main metabolic pathways (kynurenine pathway, indole pathway and serotonin/melatonin pathway) result in metabolites such as kynurenic acid, xanturenic acid, indole-3-propionic acid and serotonin/melatonin. The kynurenine pathway is regulated by indoleamine 2,3-dioxygenase (IDO), an enzyme that is upregulated by pro-inflammatory molecules such as INF, IL-6 and LPS. Higher activity of IDO is associated with increased inflammation and fibrosis in NAFLD, as well with increased glucose levels, obesity and atherosclerosis. On the other hand, increased concentrations of the indole pathway metabolites, regulated by the gut microbiome, seem to result in more favorable outcomes. This narrative review summarizes the interactions between tryptophan metabolism, the gut microbiome and the immune system as potential drivers of cardiometabolic diseases in NAFLD.

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“…Interleukin-6 family members, such as IL-6, IL-11, IL-30, IL-31, OSM, LIF, CNTF, CT-1, CT-2, and CLC, have an important role in heart disease pathogenesis as they exhibit pro-inflammatory, anti-inflammatory, and proatherogenic effects using different trans-signaling pathways [ 115 ]. IL-6 is synthesized by T lymphocytes, macrophages, and adipocytes, as well as by cardiovascular system structures such as endothelial cells, vascular smooth muscle cells, or ischemic cardiomyocytes [ 116 ].…”

Section: Biomarkers In the Diagnosis And Prognosis Of Acute Myocardia...mentioning

confidence: 99%

A Real Pandora’s Box in Pandemic Times: A Narrative Review on the Acute Cardiac Injury Due to COVID-19

Timpau

Miftode

Leca

et al. 2022

Life

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The intricate relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the cardiovascular system is an extensively studied pandemic topic, as there is an ever-increasing amount of evidence that reports a high prevalence of acute cardiac injury in the context of viral infection. In patients with Coronavirus disease 2019, COVID-19, a significant increase in serum levels of cardiac troponin or other various biomarkers was observed, suggesting acute cardiac injury, thus predicting both a severe course of the disease and a poor outcome. Pathogenesis of acute cardiac injury is not yet completely elucidated, though several mechanisms are allegedly involved, such as a direct cardiomyocyte injury, oxygen supply-demand inequity caused by hypoxia, several active myocardial depressant factors during sepsis, and endothelial dysfunction due to the hyperinflammatory status. Moreover, the increased levels of plasma cytokines and catecholamines and a significantly enhanced prothrombotic environment may lead to the destabilization and rupture of atheroma plaques, subsequently triggering an acute coronary syndrome. In the present review, we focus on describing the epidemiology, pathogenesis, and role of biomarkers in the diagnosis and prognosis of patients with acute cardiac injury in the setting of the COVID-19 pandemic. We also explore some novel therapeutic strategies involving immunomodulatory therapy, as well as their role in preventing a severe form of the disease, with both the short-term outcome and the long-term cardiovascular sequelae being equally important in patients with SARS-CoV-2 induced acute cardiac injury.

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The Role of Interleukin-6 Family Members in Cardiovascular Diseases

Cited by 52 publications

References 187 publications

Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients

Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

A Real Pandora’s Box in Pandemic Times: A Narrative Review on the Acute Cardiac Injury Due to COVID-19

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