The Potential Role of Cytokine Storm Pathway in the Clinical Course of Viral Respiratory Pandemic.

Giuseppe Murdaca,Stefania Isola,Francesca Paladin,Alessandro Tonacci,Alessandro Allegra,Sebastiano Gangemi

doi:10.3390/biomedicines9111688

Abstract

The “cytokine storm” (CS) consists of a spectrum of different immune dysregulation disorders characterized by constitutional symptoms, systemic inflammation and multiorgan dysfunction triggered by an uncontrolled immune response. Particularly in respiratory virus infections, the cytokine storm plays a primary role in the pathogenesis of respiratory disease and the clinical outcome of respiratory diseases, leading to complications such as alveolar edema and hypoxia. In this review, we wanted to analyze the different pathogenetic mechanisms involved in the various respiratory viral pandemics (COVID-19; SARS; MERS; H1N1 influenza A and Spanish flu) which have affected humans in this and last century, with particular attention to the phenomenon of the “cytokine storm” which determines the clinical severity of the respiratory disease and consequently its lethality.

Highlights

CXCL8 chemokine is involved in the inflammation and trafficking of immune cells in the context of viral infections, as it has a chemotactic action for neutrophils and monocytes in the respiratory tract [5]
Considering the crucial role proinflammatory pathogeneticpathogenetic mechanismsmechanisms in severe in sev Considering theofcrucial role of proinflammatory viral infectionsviral affecting the respiratory tract, we believe that greaterthat knowledge these infections affecting the respiratory tract, weabelieve a greaterof knowledge of th processes could allow us to identify, the most suitable treatment, and the strategies to be prepared for the viral pandemic
Anti-IL6 monoclonal antibodies tocilizumab, siltuximab and sarilumab are currently being studied in the management of severe COVID-19 [110]

Summary

Introduction

Respiratory viral infection results in the activation and recognition by cytotoxic T lymphocytes, resulting in the overproduction of a wide range of proinflammatory mediators (IL-1β, IFN-γ, IP-10, monocyte chemotactic protein 1 (MCP-1) and IL-17), in addition to the activation of basophils and mast cells, causing microvascular losses and a procoagulative state. It is in this context that the “cytokine storm” syndrome develops, the main actor involved in the clinical severity of respiratory infection, up to acute respiratory distress syndrome (ARDS) [1]. The results of this review highlight the importance of the cytokine storm during the infection of these pandemic viruses, suggesting that this condition must be considered as a relevant factor in the election of medical treatments for these viral diseases

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Conclusion