IMMUNOPATHOLOGY AND IMMUNOPHARMACOTHERAPY OF CORONAVIRUS DISEASE 2019 (COVID-19): FOCUS ON INTERLEUKIN 6

2020 ◽  
Vol 58 (3) ◽  
pp. 245-261 ◽  
Author(s):  
E. L. Nasonov
Keyword(s):  
Interleukin 6 ◽  
Prognostic Value ◽  
Macrophage Activation ◽  
Critical Conditions ◽  
Malignant Neoplasms ◽  
Inflammatory Rheumatic Diseases ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Immune Mediated

The Coronavirus Disease 2019 (COVID-19) pandemic has drawn closer attention than ever before to the problems of the immunopathology of human diseases, many of which have been reflected when studying immune-mediated inflammatory rheumatic diseases (IIRDs). The hyperimmune response called a cytokine storm, the pathogenetic subtypes of which include hemophagocytic lymphohistiocytosis, macrophage activation syndrome, and cytokine release syndrome, is among the most serious complications of IIRDs or treatment for malignant neoplasms and may be a stage of COVID-19 progression. A premium is placed to interleukin-6 (IL-6) in the spectrum of cytokines involved in the pathogenesis of the cytokine storm syndrome. The clinical introduction of monoclonal antibodies (mAbs) that inhibit the activity of this cytokine (tocilizumab, sarilumab, etc.) is one of the major advances in the treatment of IIRDs and critical conditions within the cytokine storm syndrome in COVID-19. The review discusses data on the clinical and prognostic value of IL-6 and the effectiveness of anti-IL-6 receptor and anti-IL-6 mAbs, as well as prospects for personalized therapy of the cytokine storm syndrome in COVID-19.

scholarly journals Macrophage Activation and Cytokine Release Syndrome in COVID-19: Current Updates and Analysis of Repurposed and Investigational Anti-Cytokine Drugs

Drug Research ◽  
2021 ◽  
Author(s):  
Ashif Iqubal ◽  
Farazul Hoda ◽  
Abul Kalam Najmi ◽  
Syed Ehtaishamul Haque
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Macrophage Activation ◽  
Fatality Rate ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Disease Condition ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

AbstractCoronavirus disease (COVID-19) emerged from Wuhan, has now become pandemic and the mortality rate is growing exponentially. Clinical complication and fatality rate is much higher for patients having co-morbid issues. Compromised immune response and hyper inflammation is hall mark of pathogenesis and major cause of mortality. Cytokine release syndrome (CRS) or cytokine storm is a term used to affiliate the situation of hyper inflammation and therefore use of anti-cytokine and anti-inflammatory drugs is used to take care of this situation. Looking into the clinical benefit of these anti-inflammatory drugs, many of them enter into clinical trials. However, understanding the immunopathology of COVID-19 is important otherwise, indiscriminate use of these drugs could be fetal as there exists a very fine line of difference between viral clearing cytokines and inflammatory cytokines. If any drug suppresses the viral clearing cytokines, it will worsen the situation and hence, the use of these drugs must be based on the clinical condition, viral load, co-existing disease condition and severity of the infection.

scholarly journals Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1067
Author(s):  
Oleksandr Oliynyk ◽  
Wojciech Barg ◽  
Anna Slifirczyk ◽  
Yanina Oliynyk ◽  
Vitaliy Gurianov ◽  
...  
Keyword(s):  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
C Reactive Protein ◽  
Treatment Results ◽  
Reactive Protein ◽  
Median Serum ◽  
D Dimer

Background: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. Methods: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In the MAS and CRS groups, treatment results were assessed depending on whether or not tocilizumab was used. Results: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/mL, p < 0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p = 0.043), RR = 2.1 (95% CI 1.0–4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p = 0.013), RR = 0.50 (95% CI 0.25–0.99). Сonclusions: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients, it contributed to reduced mortality.

scholarly journals Artesunate may attenuate the effects of Cytokine Release Syndrome (CRS) in Covid-19 Disease by targeting Interleukin-6 and associated inflammatory response pathways

2020 ◽  
Author(s):  
Yolanda Augustin ◽  
Henry Staines ◽  
Adeeba Kamarulzaman ◽  
Henry Staines ◽  
Sanjeev Krishna
Keyword(s):  
Organ Failure ◽  
Interleukin 6 ◽  
Inflammatory Cytokine ◽  
The Novel ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Multi Organ Failure ◽  
History Of ◽  
Global Health Challenge

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented global health challenge for which safe, effective and affordable treatments need to be rapidly identified. Although in the majority of patients, the natural history of COVID-19 infection is self limiting, a small proportion of patients develop a cytokine release syndrome (CRS)/cytokine storm (CS) with raised Interleukin-6 (IL-6) and associated inflammatory cytokines. Dysregulated continual synthesis of IL-6 can contribute to multi-organ failure (MOF). Artesunate is an established antimalarial with an excellent tolerability and safety profile. Artesunate is able to modulate pro-inflammatory cytokine pathways and in doing so prevent multi-organ failure in models of lung, myocardial and renal injury in a number of cell line and animal models. Robust clinical trials are indicated to test this hypothesis.

scholarly journals Coronavirus disease-2019 (COVID-19): value of IL-6 inhibitors

2020 ◽  
Vol 30 (5) ◽  
pp. 629-644
Author(s):  
E. L. Nasonov
Keyword(s):  
Distress Syndrome ◽  
Drug Repurposing ◽  
Biologic Agents ◽  
Critical Conditions ◽  
Inflammatory Rheumatic Diseases ◽  
Cytokine Storm ◽  
Efficacy And Safety ◽  
Immune Mediated ◽  
Inflammatory Drugs ◽  
Clinical Problems

The coronavirus disease 2019 (COVID-19) pandemic has drawn attention to new clinical and fundamental issues in the immunopathology of human diseases. Since in COVID-19 it is the ‘‘hyperimmune’’ response, called cytokine storm syndrome, which forms the basis of the pathogenesis of acute respiratory distress syndrome (ARDS) and multiorgan dysfunction in COVID-19, special attention is drawn to the possibility of “repurposing” (drug repurposing) of some widely used for treatment immune-mediated inflammatory rheumatic diseases (IMIRDs) anti-inflammatory drugs, including glucocorticoids (GC), disease-modified anti-rheumatic drugs (DMARDs), biologic agents and ‘‘targeted’’ DMARDs. In the spectrum of cytokines involved in the pathogenesis of cytokine storm syndrome in IMIRDs and COVID-19, great importance is attached to the pro-inflammatory cytokine, interleukin IL-6. The development and introduction into clinical practice of monoclonal antibodies (mAbs) that inhibit the activity of IL-6 are among the major advances in the treatment of IMIRDs, and in recent years, critical conditions within the framework of the cytokine storm syndrome, including in COVID-19. The review discusses the materials of numerous studies devoted to the problems of the efficacy and safety of mAbs to the IL-6 receptor (tocilizumab) and other mAbs that inhibit the activity of this cytokine in COVID-19. Despite the effectiveness of inhibiting IL-6 in patients with severe COVID-19, many theoretical and clinical problems of immunopathology and pharmacotherapy of this disease require further study.

scholarly journals Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome.

2021 ◽  
Author(s):  
Oleksandr Oliynyk ◽  
Wojciech Barg ◽  
Anna Slifirczyk ◽  
Yanina Oliynyk ◽  
Vitaliy Gurianov ◽  
...  
Keyword(s):  
Group Treatment ◽  
Macrophage Activation ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
C Reactive Protein ◽  
Treatment Results ◽  
Reactive Protein ◽  
Median Serum ◽  
D Dimer

Background: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. Methods: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In each group, treatment results were assessed depending on whether or not tocilizumab was used. Results: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/ml, p &amp;lt;0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p=0.043), RR = 2.1 (95% CI 1.0-4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p=0.013), RR = 0.50 (95% CI 0.25-0.99). Сonclusions: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients it contributed to reduced mortality.

Systematic Review on Treatment Trials of Tocilizumab- A Repurposing Drug Against COVID-19

2021 ◽  
Vol 16 ◽  
Author(s):  
Shilpita Banerjee ◽  
Ajit Kumar Mahapatra
Keyword(s):  
Individual Patient Data ◽  
Critical Conditions ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Health Crisis ◽  
Randomized Controlled ◽  
Global Issue ◽  
Humanized Monoclonal Antibody ◽  
Integral Role ◽  
Rate Of Recovery

Background: Coronavirus disease (COVID-19) that is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a global issue today. There exists an ongoing health crisis all over the world and efficacious drugs against COVID-19 are not available yet. Therefore, on an urgent basis, scientists are looking for safe and efficacious drugs against SARS-CoV-2. Methods: The reported individual patient data and clinical outcomes including rate of recovery and mortality, patients’ characteristics and complications are reviewed. Randomized controlled trials, single center cohort studies and different case studies are provided and PICO model is used to illustrate the outcomes. Results: There exists several FDA (U.S Food and Drug Administration) approved anti corona virus drugs that sometimes are unsuccessful to cure COVID-19 critical conditions. It has been observed that a humanized monoclonal antibody, Tocilizumab (licensed for the treatment of rheumatoid arthritis), targeting the interleukin-6 (IL-6) receptor, has an integral role in the treatment of COVID-19. Conclusion: The cause behind the mortality of COVID-19 patients was found to be the Cytokine Release Syndrome (CRS). So, beside other antiviral drugs, the utilization of tocilizumab should also be considered as it can effectively block IL-6 and reduce the inflammatory signal.

scholarly journals CD40 agonist-induced IL-12p40 potentiates hepatotoxicity

2020 ◽  
Vol 8 (1) ◽  
pp. e000624
Author(s):  
Caroline Bonnans ◽  
Graham Thomas ◽  
Wenqian He ◽  
Breanna Jung ◽  
Wei Chen ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Inflammatory Cytokine ◽  
Liver Enzymes ◽  
Historical Data ◽  
Primary Sources ◽  
Liver Pathology ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Cytokine Network ◽  
Dose Limiting Toxicity

BackgroundCD40 is a compelling target for cancer immunotherapy, however, attempts to successfully target this pathway have consistently been hampered by dose-limiting toxicity issues in the clinic that prevents the administration of efficacious doses.MethodsHere, using cytokine and cytokine receptor depletion strategies in conjunction with a potent CD40 agonist, we investigated mechanisms underlying the two primary sources of CD40 agonist-associated toxicity, hepatotoxicity and cytokine release syndrome (CRS).ResultsWe demonstrate that CD40 agonist -induced hepatotoxicity and CRS are mechanistically independent. Historical data have supported a role for interleukin-6 (IL-6) in CRS-associated wasting, however, our findings instead show that an inflammatory cytokine network involving TNF, IL-12p40, and IFNγ underlie this process. Deficiency of TNF or IFNγ did not influence CD40-induced hepatitis however loss of IL-12p40 significantly decreased circulating concentrations of liver enzymes and reduced the frequency of activated CD14+MHCII+myeloid cells in the liver, indicating a role for IL-12p40 in liver pathology.ConclusionsAs clinical research programs aim to circumnavigate toxicity concerns while maintaining antitumor efficacy it will be essential to understand which features of CD40 biology mediate antitumor function to develop both safe and efficacious agonists.

Sign in / Sign up

Export Citation Format

Share Document