IL-33 in COVID-19: friend or foe?

摘要

The COVID-19 pandemic,caused by the highly transmissible and pathogenic severe acute respiratory syndrome coronavirus 2(SAR-CoV-2),has led to more than 2.7 million deaths worldwide as of March 2021.Although considerable efforts are underway to reveal the immunopathology of COVID-19,the key factors and processes that initiate hyperinflammatory responses and cause severe clinical outcomes in certain individuals remain unclear.The damage-associated molecular pattern(DAMP)molecule IL-33 belongs to the IL-1 family and has been recognized as an alarmin that indicates cellular damage or infection.Full-length IL-33 requires cleavage by proteases to generate its mature bioactive form,which can bind to the ST2 receptor(also known as IL-1RL1),leading to activation of the NF-κB pathway in various innate and adaptive immune cells.The relatively high abundance of IL-33 in epithelial and endothelial cells accounts for its proinflammatory role in respiratory diseases.1 Recent observations have revealed that serum IL-33 is upregulated in elderly patients with COVID-19 and associated with adverse outcomes.