scholarly journals Cytokine release syndrome (CRS) and nicotine in COVID-19 patients: trying to calm the storm

2020 ◽  
Author(s):  
Jesus Gonzalez-Rubio ◽  
Carmen Navarro ◽  
Elena Lopez-Najera ◽  
Ana Lopez-Najera ◽  
Lydia Jimenez-Diaz ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Proinflammatory Cytokine ◽  
Acetylcholine Receptors ◽  
Signal Transduction Pathway ◽  
Evidence Based ◽  
Transduction Pathway ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Epidemiological Evidence ◽  
Pro Inflammatory Cytokines

SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes a severe acute respiratory syndrome (COVID-19), fatal in many cases, characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severe patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being searched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, we hypothesize that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients.

scholarly journals Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

2021 ◽  
Vol 22 (15) ◽  
pp. 7914
Author(s):  
So Yeong Cheon ◽  
Bon-Nyeo Koo
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Response ◽  
Immune Complex ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Organ Damage ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Pro Inflammatory Cytokines

The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm—elevated levels of hyperactivated immune cells—and circulating pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1β and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.

scholarly journals Nicotinic Receptor Interloop Proline Anchors β1-β2 and Cys loops in Coupling Agonist Binding to Channel Gating

2008 ◽  
Vol 132 (2) ◽  
pp. 265-278 ◽  
Author(s):  
Won Yong Lee ◽  
Chris R. Free ◽  
Steven M. Sine
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Single Channel ◽  
Channel Gating ◽  
Site Directed Mutagenesis ◽  
Structural Basis ◽  
Transduction Pathway ◽  
Diverse Range ◽  
Channel Opening ◽  
Central Nervous Systems

Nicotinic acetylcholine receptors (AChRs) mediate rapid excitatory synaptic transmission throughout the peripheral and central nervous systems. They transduce binding of nerve-released ACh into opening of an intrinsic channel, yet the structural basis underlying transduction is not fully understood. Previous studies revealed a principal transduction pathway in which αArg 209 of the pre-M1 domain and αGlu 45 of the β1–β2 loop functionally link the two regions, positioning αVal 46 of the β1–β2 loop in a cavity formed by αPro 272 through αSer 269 of the M2–M3 loop. Here we investigate contributions of residues within and proximal to this pathway using single-channel kinetic analysis, site-directed mutagenesis, and thermodynamic mutant cycle analysis. We find that in contributing to channel gating, αVal 46 and αVal 132 of the signature Cys loop couple energetically to αPro 272. Furthermore, these residues are optimized in both their size and hydrophobicity to mediate rapid and efficient channel gating, suggesting naturally occurring substitutions at these positions enable a diverse range of gating rate constants among the Cys-loop receptor superfamily. The overall results indicate that αPro 272 functionally couples to flanking Val residues extending from the β1–β2 and Cys loops within the ACh binding to channel opening transduction pathway.

scholarly journals Cytokine release syndrome: inhibition of pro-inflammatory cytokines as a solution for reducing COVID-19 mortality

2020 ◽  
Vol 31 (3) ◽  
pp. 81-93
Author(s):  
Negar Moradian ◽  
Mahdi Gouravani ◽  
Mohammad Amin Salehi ◽  
Arash Heidari ◽  
Melika Shafeghat ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Pro Inflammatory Cytokines

scholarly journals An anti-CD6 antibody for the treatment of COVID-19 patients with cytokine-release syndrome: report of three cases

Immunotherapy ◽  
2021 ◽  
Author(s):  
Lázaro Manuel Filgueira ◽  
Julio Betancourt Cervantes ◽  
Orlando Adolfo Lovelle ◽  
Carlos Herrera ◽  
Carlos Figueredo ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Inflammatory Cytokine ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Activated T Cells ◽  
Access Protocol ◽  
Tnf Α ◽  
Ifn Γ ◽  
Syndrome Report ◽  
Pro Inflammatory Cytokines

In COVID-19, the inflammatory cytokine-release syndrome is associated with the progression of the disease. Itolizumab is a monoclonal antibody that recognizes human CD6 expressed in activated T cells. The antibody has shown to be safe and efficacious in the treatment of moderate to severe psoriasis. Its effect is associated with the reduction of pro-inflammatory cytokines release, including IFN-γ, IL-6 and TNF-α. Here, we report the outcome of three severe and critically ill COVID-19 patients treated with itolizumab as part of an expanded access protocol. Itolizumab was able to reduce IL-6 concentrations in all the patients. Two of the three patients showed respiratory and radiological improvement and were fully recovered. We hypothesize this anti-inflammatory therapy in addition to antiviral and anticoagulant therapy could reduce COVID-19 associated morbidity and mortality.

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