scholarly journals COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm

2020 ◽  
Vol 2020 ◽  
pp. 1-34
Author(s):  
Patrick C. Bradshaw ◽  
William A. Seeds ◽  
Alexandra C. Miller ◽  
Vikrant R. Mahajan ◽  
William M. Curtis
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
T Cell ◽  
Energy Metabolism ◽  
Respiratory Distress ◽  
Ketogenic Diet ◽  
Innate Immune Response ◽  
Redox State ◽  
Innate Immune ◽  
Cytokine Storm

Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of (R)-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity. Limitations of the proposed therapy include the following: it is unknown if human immune and lung cell functions are enhanced by ketosis, the risk of ketoacidosis must be assessed prior to initiating treatment, and permissive dietary fat and carbohydrate levels for exogenous ketones to boost immune function are not yet established. The third limitation could be addressed by studies with influenza-infected mice. A clinical study is warranted where COVID-19 patients consume a permissive diet combined with ketone ester to raise blood ketone levels to 1 to 2 mM with measured outcomes of symptom severity, length of infection, and case fatality rate.

scholarly journals Still’s Disease in the Constellation of Hyperinflammatory Syndromes: A Link with Kawasaki Disease?

2021 ◽  
Vol 10 (15) ◽  
pp. 3244
Author(s):  
Perrine Dusser ◽  
Isabelle Koné-Paut
Keyword(s):  
Immune Response ◽  
Kawasaki Disease ◽  
Innate Immune Response ◽  
Adaptive Response ◽  
Genetic Factors ◽  
Innate Immune ◽  
Cytokine Storm ◽  
Still’S Disease ◽  
Still's Disease ◽  
Excessive Activation

Still’s disease and Kawasaki disease (KD) today belong to the group of cytokine storm syndromes, a pathophysiological set related to excessive activation of the innate immune response. We present here a personal vision of what can link these two diseases, taking up their concepts at their beginning. By their many clinical and physiopathological similarities, we conclude that they constitute a common spectrum whose fate is modified by subtle differences in terms of adaptive response that could, in part, be driven by genetic factors.

scholarly journals Longitudinal single-cell immune profiling revealed distinct innate immune response in asymptomatic COVID-19 patients

2020 ◽  
Author(s):  
Xiang-Na Zhao ◽  
Yue You ◽  
Guo-Lin Wang ◽  
Hui-Xia Gao ◽  
Xiao-Ming Cui ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Innate Immune Response ◽  
Clonal Expansion ◽  
Innate Immune ◽  
Type I ◽  
Severe Condition ◽  
Asymptomatic Patients

SUMMARYRecent studies have characterized the single-cell immune landscape of host immune response of coronavirus disease 2019 (COVID-19), specifically focus on the severe condition. However, the immune response in mild or even asymptomatic patients remains unclear. Here, we performed longitudinal single-cell transcriptome sequencing and T cell/B cell receptor sequencing on 3 healthy donors and 10 COVID-19 patients with asymptomatic, moderate, and severe conditions. We found asymptomatic patients displayed distinct innate immune responses, including increased CD56briCD16− NK subset, which was nearly missing in severe condition and enrichment of a new Th2-like cell type/state expressing a ciliated cell marker. Unlike that in moderate condition, asymptomatic patients lacked clonal expansion of effector CD8+ T cells but had a robust effector CD4+ T cell clonal expansion, coincide with previously detected SARS-CoV-2-reactive CD4+ T cells in unexposed individuals. Moreover, NK and effector T cells in asymptomatic patients have upregulated cytokine related genes, such as IFNG and XCL2. Our data suggest early innate immune response and type I immunity may contribute to the asymptomatic phenotype in COVID-19 disease, which could in turn deepen our understanding of severe COVID-19 and guide early prediction and therapeutics.

scholarly journals The Regulation of the CNS Innate Immune Response Is Vital for the Restoration of Tissue Homeostasis (Repair) after Acute Brain Injury: A Brief Review

2010 ◽  
Vol 2010 ◽  
pp. 1-18 ◽  
Author(s):  
M. R. Griffiths ◽  
P. Gasque ◽  
J. W. Neal
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
T Cell ◽  
Innate Immune Response ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tissue Homeostasis ◽  
Innate Immune ◽  
Apoptotic Cells ◽  
Treg Population

Neurons and glia respond to acute injury by participating in the CNS innate immune response. This involves the recognition and clearance of “not self ” pathogens and “altered self ” apoptotic cells. Phagocytic receptors (CD14, CD36, TLR–4) clear “not self” pathogens; neurons and glia express “death signals” to initiate apoptosis in T cells.The complement opsonins C1q, C3, and iC3b facilitate the clearance of apoptotic cells by interacting with CR3 and CR4 receptors. Apoptotic cells are also cleared by the scavenger receptors CD14, Prs-R, TREM expressed by glia. Serpins also expressed by glia counter the neurotoxic effects of thrombin and other systemic proteins that gain entry to the CNS following injury. Complement pathway and T cell activation are both regulated by complement regulatory proteins expressed by glia and neurons. CD200 and CD47 are NIRegs expressed by neurons as “don't eat me” signals and they inhibit microglial activity preventing host cell attack. Neural stem cells regulate T cell activation, increase the Treg population, and suppress proinflammatory cytokine expression. Stem cells also interact with the chemoattractants C3a, C5a, SDF-1, and thrombin to promote stem cell migration into damaged tissue to support tissue homeostasis.

scholarly journals Strong innate immune response and cell death in chicken splenocytes infected with genotype VIId Newcastle disease virus

2012 ◽  
Vol 9 (1) ◽  
pp. 208 ◽  
Author(s):  
Zenglei Hu ◽  
Jiao Hu ◽  
Shunlin Hu ◽  
Xiaowen Liu ◽  
Xiaoquan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Innate Immune Response ◽  
Newcastle Disease ◽  
Innate Immune

R-type anion channel activation is an essential step for ROS-dependent innate immune response in Arabidopsis suspension cells

2009 ◽  
Vol 36 (9) ◽  
pp. 832 ◽  
Author(s):  
Jean Colcombet ◽  
Yves Mathieu ◽  
Remi Peyronnet ◽  
Nicolas Agier ◽  
Françoise Lelièvre ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Innate Immune Response ◽  
Xanthomonas Campestris ◽  
Plant Defence ◽  
Anion Channel ◽  
Innate Immune ◽  
Channel Blockers ◽  
Ros Production ◽  
Suspension Cells

Plants are constantly exposed to environmental biotic and abiotic stresses. Plants cells perceive these factors and trigger early responses followed by delayed and complex adaptation processes. Using cell suspensions of Arabidopsis thaliana (L.) as a cellular model, we investigated the role of plasma membrane anion channels in Reactive Oxygen Species (ROS) production and in cell death which occurs during non-host pathogen infection. Protoplasts derived from Arabidopsis suspension cells display two anion currents with characteristics very similar to those of the slow nitrate-permeable (S-type) and rapid sulfate-permeable (R-type) channels previously characterised in hypocotyl cells and other cell types. Using seven inhibitors, we showed that the R-type channel and ROS formation in cell cultures present similar pharmacological profiles. The efficiency of anion channel blockers to inhibit ROS production was independent of the nature of the triggering signal (osmotic stress or general elicitors of plant defence), indicating that the R-type channel represents a crossroad in the signalling pathways leading to ROS production. In a second step, we show that treatment with R-type channel blockers accelerates cell death triggered by the non-specific plant pathogen Xanthomonas campestris. Finally, we discuss the hypothesis that the R-type channel is involved in innate immune response allowing cell defence via antibacterial ROS production.

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