scholarly journals Cytokine Storm, Corticosteroids and İnterleukin-6 Receptor Antibodies in Context of Antiinflammatory Treatment in COVID-19

2020 ◽  
pp. 67-75
Author(s):  
Ozgur Karcioglu ◽  
Goksu Afacan ◽  
Bilgen Ozkaya ◽  
Ebru Yilmaz ◽  
Eylem Ersan ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Viral Infections ◽  
Signs And Symptoms ◽  
Clinical Findings ◽  
Rapid Progression ◽  
Cytokine Storm ◽  
Inflammatory Status ◽  
Interleukin 6 Receptor ◽  
Short Time ◽  
Receptor Antibodies

It is well established that cytokine storm is associated with more severe clinical course of COVID-19. Many clinical findings of COVID-19 and other severe viral infections (e.g. fever, muscle pain, respiratory distress, cough), are directly attributed to cytokine storm. For example, IL-6 and IL-10 can be used as predictors for expedient diagnosis of patients with higher risk of deterioration. Hyper-inflammatory status in patients with severe COVID-19 is to be mitigated to alleviate signs and symptoms in cytokine storm. In case of deterioration of oxygenation and rapid progression of imaging (CT) findings, glucocorticoids can be used for a short time (3-5 days) for patients in whom overactivation of the body's inflammatory response is suspected. On the other hand, interleukin-6 receptor antibodies tocilizumab, sarilumab, siltuximab can be used as immunomodulators, to suppress inflammation and to alleviate fever and other manifestations of immune response. Their beneficial efficacy is especially remarkable during the cytokine storm period. It should be kept in mind that the agents to be used in the management of any given patient should be tailored for each situation.

scholarly journals On the role of bacterial metalloproteases in COVID-19 associated cytokine storm

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
László Földvári-Nagy ◽  
Tamás Schnabel ◽  
Gabriella Dörnyei ◽  
Tamás Korcsmáros ◽  
Katalin Lenti
Keyword(s):  
Mortality Rate ◽  
Interleukin 6 ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Membrane Receptors ◽  
Critical Element ◽  
Cytokine Storm ◽  
Interleukin 6 Receptor ◽  
Membrane Bound ◽  
Prophylactic Use

AbstractThe cytokine release syndrome or cytokine storm, which is the hyper-induction of inflammatory responses has a central role in the mortality rate of COVID-19 and some other viral infections. Interleukin-6 (IL-6) is a key player in the development of cytokine storms. Shedding of interleukin-6 receptor (IL-6Rα) results in the accumulation of soluble interleukin-6 receptors (sIL-6R). Only relatively few cells express membrane-bound IL-6Rα. However, sIL-6R can act on potentially all cells and organs through the ubiquitously expressed gp130, the coreceptor of IL-6Rα. Through this, so-called trans-signaling, IL-6–sIL-6R is a powerful factor in the development of cytokine storms and multiorgan involvement. Some bacteria (e.g., Serratia marcescens, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes), commonly considered to cause co-infections during viral pneumonia, can directly induce the shedding of membrane receptors, including IL-6Rα, or enhance endogenous shedding mechanisms causing the increase of sIL-6R level. Here we hypothesise that bacteria promoting shedding and increase the sIL-6R level can be an important contributing factor for the development of cytokine storms. Therefore, inhibition of IL-6Rα shedding by drastically reducing the number of relevant bacteria may be a critical element in reducing the chance of a cytokine storm. Validation of this hypothesis can support the consideration of the prophylactic use of antibiotics more widely and at an earlier stage of infection to decrease the mortality rate of COVID-19.

scholarly journals Tocilizumab Contributes to the Inflammatory Status of Mature Dendritic Cells through Interleukin-6 Receptor Subunits Modulation

2017 ◽  
Vol 8 ◽  
Author(s):  
Daniel Meley ◽  
Audrey Héraud ◽  
Valerie Gouilleux-Gruart ◽  
Fabrice Ivanes ◽  
Florence Velge-Roussel
Keyword(s):  
Dendritic Cells ◽  
Interleukin 6 ◽  
Inflammatory Status ◽  
Interleukin 6 Receptor

SAT0076 Comparison of anti-interleukin-6 and anti-interleukin-6 receptor antibodies using in vivo functional systems

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 495.3-495
Author(s):  
S. Shaw ◽  
D. Marshall ◽  
H. Neale ◽  
K. Kretsos ◽  
T. Bourne ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Functional Systems ◽  
Interleukin 6 Receptor ◽  
Receptor Antibodies

scholarly journals In vitro selection of an RNA aptamer yields an interleukin-6/interleukin-6 receptor interaction inhibitor

2021 ◽  
Author(s):  
Takehiro Ando ◽  
Mizuki Yamamoto ◽  
Yukio Takamori ◽  
Keita Tsukamoto ◽  
Daisuke Fuji ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
In Vitro Selection ◽  
Receptor Interaction ◽  
Rna Aptamer ◽  
Cytokine Storm ◽  
Interleukin 6 Receptor ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Selection Of

ABSTRACT Interleukin-6 (IL-6) binds to IL-6 receptor (IL-6R) subunit, related to autoimmune diseases and cytokine storm in COVID-19. In this study we performed Systematic Evolution of Ligands by Exponential enrichment (SELEX) and identified a novel RNA aptamer. This RNA aptamer not only bound to IL-6R with a dissociation constant of 200 nM, but also inhibited the interaction of IL-6R with IL-6.

scholarly journals Recovery of respiratory function in mdx mice co-treated with neutralizing interleukin-6 receptor antibodies and urocortin-2

2018 ◽  
Vol 596 (21) ◽  
pp. 5175-5197 ◽  
Author(s):  
David P. Burns ◽  
Leonie Canavan ◽  
Jane Rowland ◽  
Robin O'Flaherty ◽  
Molly Brannock ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Respiratory Function ◽  
Mdx Mice ◽  
Interleukin 6 Receptor ◽  
Receptor Antibodies

scholarly journals Use of tocilizumab in the combination treatment of a COVID-19 patient with concomitant rheumatoid arthritis (a case report)

2021 ◽  
Vol 23 (5) ◽  
pp. 739-748
Author(s):  
V. A. Vizir ◽  
A. S. Sadomov ◽  
O. V. Demidenko
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibody ◽  
Combination Treatment ◽  
Interleukin 6 ◽  
Clinical Case ◽  
Clinical Laboratory ◽  
Cytokine Storm ◽  
X Ray ◽  
Interleukin 6 Receptor ◽  
Receptor Monoclonal Antibody

The aim is to familiarize practitioners with the clinical case of tocilizumab use in the combination treatment of the coronavirus disease (COVID-19) patient with concomitant rheumatoid arthritis. Materials and methods. The clinical case shows our own follow-up of COVID-19 clinical course in the patient with concomitant rheumatoid arthritis during combination treatment with the use of a recombinant humanized anti-interleukin-6 receptor monoclonal antibody tocilizumab. Results. The patient with a severe COVID-19 course, whose examination and treatment results are given in the article, was comorbid for rheumatoid arthritis. The cytokine storm development at the hospital stage was confirmed by an increase in markers of systemic inflammation: C-reactive protein, D-dimer, fibrinogen, an almost 50-fold increase in serum interleukin-6 level, as well as absolute and relative lymphocytopenia. Despite the anti-inflammatory therapy administered with systemic corticosteroids, the patient’s condition progressively worsened. After assessing the indications and contraindications, it was decided to use the interleukin-6 receptor inhibitor tocilizumab, followed by rapid clinical, laboratory and X-ray positive response to the treatment. The understanding of tocilizumab use in patients with COVID-19 at the current stage was formed based on the comparative analysis of our own clinical case data and the results of relevant clinical trials, world recommendations and guidelines. Conclusions. The use of recombinant humanized anti-interleukin-6 receptor monoclonal antibody tocilizumab in the combination treatment of severe COVID-19 with concomitant rheumatoid arthritis is pathogenetically based and decreases the main clinical and laboratory signs of cytokine storm, respiratory failure, improves chest x-ray findings and reduces the length of hospital stay. Further large randomized placebo-controlled trials including the population of patients with various comorbid conditions are needed to clarify conclusively the place and role of anti-cytokine drugs in the treatment of COVID-19 patients.

scholarly journals In Silico Studies on Psilocybin Drug Derivatives Against SARS-CoV-2 and Cytokine Storm of Human Interleukin-6 Receptor

2022 ◽  
Vol 12 ◽  
Author(s):  
Faez Iqbal Khan ◽  
Fakhrul Hassan ◽  
Dakun Lai
Keyword(s):  
Free Energy ◽  
Structural Dynamics ◽  
Interleukin 6 ◽  
In Silico ◽  
Chemotherapeutic Agents ◽  
Cytokine Storm ◽  
Anticancer Properties ◽  
In Silico Studies ◽  
Interleukin 6 Receptor ◽  
Different Sources

Various metabolites identified with therapeutic mushrooms have been found from different sources and are known to have antibacterial, antiviral, and anticancer properties. Over thousands soil growth-based mushroom metabolites have been discovered, and utilized worldwide to combat malignancy. In this study, psilocybin-mushroom that contains the psychedelic compounds such as psilacetin, psilocin, and psilocybine were screened and found to be inhibitors of SARS-CoV-2 Mprotease. It has been found that psilacetin, psilocin, and psilocybine bind to Mprotease with −6.0, −5.4, and −5.8 kcal/mol, respectively. Additionally, the psilacetin was found to inhibit human interleukin-6 receptors to reduce cytokine storm. The binding of psilacetin to Mprotease of SARS-CoV-2 and human interleukin-6 receptors changes the structural dynamics and Gibbs free energy patterns of proteins. These results suggested that psilocybin-mushroom could be utilized as viable potential chemotherapeutic agents for SARS-CoV-2.

scholarly journals Restoration of pharyngeal dilator muscle force in dystrophin-deficient (mdx) mice following co-treatment with neutralizing interleukin-6 receptor antibodies and urocortin 2

2017 ◽  
Vol 102 (9) ◽  
pp. 1177-1193 ◽  
Author(s):  
David P. Burns ◽  
Jane Rowland ◽  
Leonie Canavan ◽  
Kevin H. Murphy ◽  
Molly Brannock ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Muscle Force ◽  
Mdx Mice ◽  
Dilator Muscle ◽  
Interleukin 6 Receptor ◽  
Receptor Antibodies

Anti–Interleukin 6 Receptor Antibodies Attenuate Antibody Recall Responses in a Mouse Model of Allosensitization

2014 ◽  
Vol 98 (12) ◽  
pp. 1262-1270 ◽  
Author(s):  
Irene Kim ◽  
Gordon Wu ◽  
Ning-ning Chai ◽  
Andrew S. Klein ◽  
Stanley Jordan
Keyword(s):  
Mouse Model ◽  
Interleukin 6 ◽  
Interleukin 6 Receptor ◽  
Receptor Antibodies

scholarly journals Fatal myocarditis and rhabdomyositis in a patient with stage IV melanoma treated with combined ipilimumab and nivolumab

2019 ◽  
Vol 26 (3) ◽  
Author(s):  
S. D. Saibil ◽  
L. Bonilla ◽  
H. Majeed ◽  
V. Sotov ◽  
D. Hogg ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Stage Iv ◽  
Immune Checkpoint Blockade ◽  
Advanced Melanoma ◽  
Concurrent Administration ◽  
Interleukin 6 Receptor ◽  
Correlative Studies ◽  
Receptor Antibodies ◽  
Stage Iv Melanoma ◽  
Steroid Refractory

Combination immune checkpoint blockade with concurrent administration of the anti-ctla4 antibody ipilimumab and the anti PD-1 antibody nivolumab has demonstrated impressive responses in patients with advanced melanoma and other diseases. That combination has also been associated with increased toxicity, including rare immune-related adverse events. Here we describe a case of fatal steroid-refractory myocarditis and panmyositis associated with the use of this combination in a patient with metastatic melanoma. Correlative studies indicated increased levels of serum interleukin 6 in this patient at the onset of toxicity, suggesting a possible role for anti– interleukin 6 receptor antibodies in the treatment of subsequent cases of this rare, but fatal, toxicity.

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