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 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 Influenza neuraminidase engages CD83 and promotes pulmonary injury

2020 ◽  
Author(s):  
Ning Ma ◽  
Xingjie Li ◽  
Hongyu Jiang ◽  
Yulong Dai ◽  
Guofeng Xu ◽  
...  
Keyword(s):  
Immune Response ◽  
Lung Injury ◽  
Innate Immune Response ◽  
Influenza A ◽  
Innate Immune ◽  
Cytokine Storm ◽  
Pulmonary Injury ◽  
Neuraminidase Treatment ◽  
Mediators Of Inflammation ◽  
Cytokine Levels

Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza infection results in hypercytokinemia, which is responsible for mortality and morbidity. However, the mechanism by which influenza induces hypercytokinemia is not fully understood. In this study, we established a mouse-adapted H9N2 virus MA01 to evaluate the innate immune response to influenza in the lung. MA01 infection caused high levels of cytokine release, enhanced pulmonary injury in mice, and upregulated CD83 protein in dendritic cells and macrophages in the lung. Influenza neuraminidase unmasked CD83 protein and contributed to high cytokine levels. Furthermore, we provide evidence that CD83 is a sialylated glycoprotein. Neuraminidase treatment enhanced LPS-stimulated NF-κB activation in RAW264.7 cells. Anti-CD83 treatment alleviated influenza virus-induced lung injury in mice. Our study indicates that influenza neuraminidase modulates CD83 status and contributes to the “cytokine storm”, which may suggest a new approach to curb this immune injury. IMPORTANCE The massive release of circulating mediators of inflammation is responsible for lung injury during influenza A virus infection. This phenomenon refers to the“cytokine storm”. However, the mechanism by which influenza induces“cytokine storm” is not fully understood. In this study, we have shown that neuraminidase unmasked CD83 protein in the lung and contributed to high cytokine levels. Anti-CD83 treatment could diminish immune damage to lung tissue. The NA-CD83 axis may represent a target for an interrupt of influenza induced lung damage.

Oral Immune Activation by Disgust and Disease-Related Pictures

2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Negative Control ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Markers ◽  
Before And After ◽  
Secondary Analyses ◽  
Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

IL-17C is a mediator of respiratory epithelial innate immune response

Pneumologie ◽  
2013 ◽  
Vol 67 (S 01) ◽  
Author(s):  
P Pfeifer ◽  
M Voss ◽  
B Wonnenberg ◽  
M Bischoff ◽  
F Langer ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Respiratory Epithelial
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