ReviewInternational immunopharmacology2022
An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19).
Review in International immunopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Exercise and Cardiovascular Risk Modulation in Post-COVID Syndrome.Current atherosclerosis reports · 2026Review
- Interleukin-6 in complications of prematurity: from biomarker to targeted therapy.Frontiers in pediatrics · 2026Review
- Beyond rejection: engineering immune responses to redefine skin graft survival.Frontiers in immunology · 2026Review
- A Modular Mathematical Model of the Immune Response for Investigating the Pathogenesis of Infectious Diseases.Viruses · 2025Article
- Identification ofMolecules (Basel, Switzerland) · 2025Article
- Longitudinal Analysis of Traditional Inflammatory Markers (IL-6, CRP) Juxtaposed With Heparin-Binding Protein (HBP) and Serum Amyloid A Protein Component (SAA) During Acute Infection and Convalescence From COVID-19 Infection in the Context of Initial Viral Load and Markers of Tissue Destruction.Journal of immunology research · 2025Article
- Evaluation of interleukin-1 and interleukin-6 receptor antagonists in a murine model of acute lung injury.Experimental physiology · 2024Article
- The role of SARS-CoV-2-mediated NF-κB activation in COVID-19 patients.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- High interleukin-6 levels induced by COVID-19 pneumonia correlate with increased circulating follicular helper T cell frequency and strong neutralization antibody response in the acute phase of Omicron breakthrough infection.Frontiers in immunology · 2024Observational
- Effects of COVID-19 on bone fragility: a new perspective from osteoimmunological biomarkers.Frontiers in immunology · 2024Article
- Airway epithelial cells and macrophages trigger IL-6-CD95/CD95L axis and mediate initial immunopathology of COVID-19.iScience · 2023Article
- Predictive Model for Mortality in Severe COVID-19 Patients across the Six Pandemic Waves.Viruses · 2023Article
- Advances in Biomarkers for Diagnosis and Treatment of ARDS.Diagnostics (Basel, Switzerland) · 2023Review
- Mesenchymal Stem Cells in the Treatment of COVID-19.International journal of molecular sciences · 2023Review
- Enhancement of IL-6 Production Induced by SARS-CoV-2 Nucleocapsid Protein and Bangladeshi COVID-19 Patients' Sera.Viruses · 2023Article
- The Local Anaesthetic Procaine Prodrugs ProcClusterInternational journal of molecular sciences · 2023Article
- Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.Molecular aspects of medicine · 2023Review
- Influence of polymorphic variations of IFNL, HLA, and IL-6 genes in severe cases of COVID-19.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Immune evasion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); molecular approaches.Molecular immunology · 2023Review
- Biomarkers: Promising and valuable tools towards diagnosis, prognosis and treatment of Covid-19 and other diseases.Heliyon · 2023Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since 2019, COVID-19 has become the most important health dilemma around the world. The dysregulated immune response which results in ARDS and cytokine storm has an outstanding role in the progression of pulmonary damage in COVID-19. IL-6, through induction of pro-inflammatory chemokines and cytokines, is the pioneer of the hyperinflammatory condition and cytokine storm in severe COVID-19. Therefore, IL-6 pathway blockade is considered an emerging approach with high efficacy to reduce lung damage in COVID-19. This article aims to review the pleiotropic roles of the IL-6 pathway in lung damage and ARDS in severe COVID-19, and the rationale for IL-6 signaling blockade at different levels, including IL-6 soluble and membrane receptor pathways, IL-6 downstream signaling (such as JAK-STAT) inhibition, and non-specific anti-inflammatory therapeutic approaches. Recent clinical data of each method, with specific concentration on tocilizumab, along with other new drugs, such as sarilumab and siltuximab, have been discussed. Challenges of IL-6 signaling inhibition, such as the risk of superinfection and hepatic injury, and possible solutions have also been explained. Moreover, to achieve the highest efficacy, ongoing clinical trials and special clinical considerations of using different IL-6 inhibitors have been discussed in detail. Special considerations, including the appropriate timing and dosage, monotherapy or combination therapy, and proper side effect managment must be noticed regarding the clinical administration of these drugs. Future studies are still necessary to improve the productivity and unknown aspects of IL-6 signaling blockade for personalized treatment of severe COVID-19.
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