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Updated: Nov 11, 2025
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
New Decade, Old Debate: Blocking the Cytokine Pathways in Infection-Induced Cytokine Cascade
Mahrukh S Rizvi1, Alice Gallo De Moraes2
1Division of Pulmonary and Critical Care Medicine, Department of Medical Education, Weill Cornell Medicine, Doha, Qatar.
Objectives:
Our understanding of the immunopathogenesis of coronavirus disease 2019 is evolving; however, a "cytokine storm" has been implicated. Ongoing clinical trials are evaluating the value of anticytokine therapies to treat patients with coronavirus disease 2019. This review summarizes the existing literature evaluating the efficacy and safety of anticytokine therapy to tackle the dysregulated immune response to infectious pathogens, discusses potential reasons for failure, applicability to coronavirus disease 2019, and future direction.
Data Sources:
Medline, PubMed, ClinicalTrials.gov, and media reports.
Study Selection:
The studies were included by author consensus.
Data Extraction:
Data were selected for inclusion after reviewing each study by author consensus.
Data Synthesis:
"Cytokine storm" is a nonspecific term, encompassing systemic inflammatory response to infectious pathogens, autoimmune conditions, cancers, trauma, and various chemotherapies. Like bacterial sepsis, viral pathogens may fuel immunopathogenesis by inducing a dysregulated autoamplifying cytokine cascade, ultimately leading to organ injury. This narrative review discusses what we know of the immune milieu of coronavirus disease 2019 versus noncoronavirus disease 2019 sepsis and/or acute respiratory distress syndrome, summarizes the existing literature on cytokine inhibitors in patients with sepsis and/or acute respiratory distress syndrome, and discusses possible reasons for recurrent failure. In doing so, it aims to assist decisions regarding the use of anticytokine therapy in patients with coronavirus disease 2019, as many regions of the world confront the second wave of the pandemic.
Conclusions:
As ongoing clinical trials determine the efficacy and safety of anticytokine therapy in patients with coronavirus disease 2019, clinicians should uphold caution when incorporating it into treatment protocols, while maintaining focus on established evidence-based practices and the mantra of "less is more."
Insights
Anticytokine therapies aim to treat the "cytokine storm" in coronavirus disease 2019. This review examines their efficacy and safety, offering insights for clinical decisions during the pandemic.
Area of Science:
- Immunology
- Infectious Diseases
- Pharmacology
Background:
- The "cytokine storm" is a complex systemic inflammatory response implicated in severe infectious diseases, including coronavirus disease 2019 (COVID-19).
- Dysregulated cytokine cascades can lead to multi-organ injury, similar to sepsis and acute respiratory distress syndrome (ARDS).
- Anticytokine therapies are being investigated to modulate this hyperinflammatory response in COVID-19.
Purpose of the Study:
- To review the existing literature on the efficacy and safety of anticytokine therapies for infectious pathogens.
- To discuss the potential reasons for the failure of these therapies in similar conditions.
- To evaluate the applicability of anticytokine therapy for COVID-19 and guide future research.
Main Methods:
- A narrative review of studies identified through Medline, PubMed, ClinicalTrials.gov, and media reports.
- Author consensus was used for study selection and data extraction.
- Comparison of the immune milieu in COVID-19 versus non-COVID-19 sepsis and ARDS.
Main Results:
- The term "cytokine storm" is nonspecific, describing a range of hyperinflammatory conditions.
- Viral pathogens, like in bacterial sepsis, can trigger a self-amplifying cytokine cascade leading to organ damage.
- Existing literature on cytokine inhibitors in sepsis/ARDS shows mixed results and potential reasons for failure.
Conclusions:
- Clinicians should exercise caution when considering anticytokine therapy for COVID-19 patients.
- Ongoing clinical trials are crucial for determining the definitive efficacy and safety of these treatments.
- Emphasis should remain on established, evidence-based practices, adopting a "less is more" approach.
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