Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection

Hu, Ronghua; Xia, Chang-Qing; Butfiloski, Edward J.; Clare‐Salzler, Michael

doi:10.1016/j.clim.2018.06.003

Cited by 73 publications

(64 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hu et al have shown that polyinosinic:polycytidylic acid (polyI:C), a Toll-like receptor 3 (TLR3) agonist, stimulated PBMCs in HG medium (24 mM glucose), while cells cultured in LG produced significantly lower levels of type I IFNs ( 125 ). Additionally, they indicated that under these conditions PBMCs express elevated levels of IFN-γ, IL-1β, IL-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-α, RANTES/CCL5 (Regulated on Activation, Normal T cell Expressed and Secreted), and macrophage inflammatory protein (MIP)-1α ( 125 ). Hu et al have also shown that HG in T2DM patients decreases the formation, viability, differentiation and functions of osteoclasts, which are bone-resident innate immune cells ( 126 ).…”

Section: Effects Of T2dm On the Immune Systemmentioning

confidence: 99%

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

et al. 2020

View full text Add to dashboard Cite

Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro-and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.

show abstract

Section: Effects Of T2dm On the Immune Systemmentioning

confidence: 99%

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

et al. 2020

View full text Add to dashboard Cite

show abstract

“…24 Another study performed on human peripheral blood mononuclear cells and human monocyte cell lines in vitro showed that hyperglycemia suppressed IFN-1 production and that pre-exposure to high glucose concentrations rendered monocytes more sensitive to IFN-α stimulation with heightened signaling. 25 Additionally, they found that high glucose levels promoted the production of other pro-inflammatory cytokines. 25 Therefore, it is probable that patients with T2DM may have alterations in their innate immune system that promotes proinflammatory cytokines as well as having a defective host defense system against viral infections by impeding IFN-1 production and signaling.…”

Section: Increased Susceptibility Of Patients With T2dm To Infectionsmentioning

confidence: 99%

“…25 Additionally, they found that high glucose levels promoted the production of other pro-inflammatory cytokines. 25 Therefore, it is probable that patients with T2DM may have alterations in their innate immune system that promotes proinflammatory cytokines as well as having a defective host defense system against viral infections by impeding IFN-1 production and signaling.…”

Section: Increased Susceptibility Of Patients With T2dm To Infectionsmentioning

confidence: 99%

Factors leading to high morbidity and mortality of COVID‐19 in patients with type 2 diabetes

Rajpal

Rahimi

Ismail‐Beigi

2020

Journal of Diabetes

157

123

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus. Diabetes (mostly type 2 diabetes mellitus, T2DM) and hyperglycemia are among the major comorbidities in patients with COVID-19 leading to poor outcomes. Reports show that patients with diabetes and COVID-19 are at an increased risk for developing severe complications including acute respiratory distress syndrome, multi-organ failure, and death. Here we explore potential mechanistic links that could explain the observed higher morbidity and mortality in this patient population. Patients with T2DM have an underlying increased level of inflammation associated with obesity and insulin resistance in addition to other comorbidities including hypertension, obesity, cardiovascular disease, dyslipidemia, and being older. We review evidence that T2DM with hyperglycemia are among factors that lead to elevated expression of angiotensin-converting enzyme 2 (ACE2) in lungs and other tissues; ACE2 is the cellular "receptor" and port of viral entry. The preexisting chronic inflammation with augmented inflammatory response to the infection and the increasing viral load leads to extreme systemic immune response ("cytokine storm") that is strongly associated with increased severity of COVID-19. Based on the available evidence, it is recommended by a panel of experts that safe but stringent control of blood glucose, blood pressure, and lipids be carried out in patients with T2DM, measures that could potentially serve to decrease the severity of COVID-19 should these patients contract the viral infection. Once the infection occurs, then attention should be directed to proper glycemic control with use of insulin and frequent monitoring of blood glucose levels.

show abstract

“…Leptin affects fat and glucose metabolism and is linked to elevated free fatty acids and glucose levels in obesity and diabetes ( 38 ). Such high levels of glucose suppress the anti-viral type 1 IFN production in PBMCs ( 41 , 42 ) and increase the reactive oxygen species in T cells ( 43 ). Elevated free fatty acids activate TLRs, induce inflammatory cytokines in circulating monocytes and enhance inflammation in T cells ( 44 – 47 ).…”

Section: Obesity and Immune Systemmentioning

confidence: 99%

From Influenza Virus to Novel Corona Virus (SARS-CoV-2)–The Contribution of Obesity

et al. 2020

View full text Add to dashboard Cite

From the beginning of 2020, the governments and the health systems around the world are tackling infections and fatalities caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) resulting in the coronavirus disease 2019 (COVID-19). This virus pandemic has turned more complicated as individuals with co-morbidities like diabetes, cardiovascular conditions and obesity are at a high risk of acquiring infection and suffering from a more severe course of disease. Prolonged viral infection and obesity are independently known to lower the immune response and a combination can thus result in a “cytokine storm” and a substantial weakening of the immune system. With the rise in obesity cases globally, the chances that obese individuals will acquire infection and need hospitalization are heightened. In this review, we discuss why obesity, a low-grade chronic inflammation, contributes toward the increased severity in COVID-19 patients. We suggest that increased inflammation, activation of renin-angiotensin-aldosterone system, elevated adipokines and higher ectopic fat may be the factors contributing to the disease severity, in particular deteriorating the cardiovascular and lung function, in obese individuals. We look at the many lessons learnt from the 2009 H1N1 influenza A pandemic and relate it to the very little but fast incoming information that is available from the SARS-CoV-2 infected individuals with overweight and obesity.

show abstract

Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection

Cited by 73 publications

References 54 publications

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

Factors leading to high morbidity and mortality of COVID‐19 in patients with type 2 diabetes

From Influenza Virus to Novel Corona Virus (SARS-CoV-2)–The Contribution of Obesity

Contact Info

Product

Resources

About