TY - JOUR
AU - Scott, Ian C.
AU - van Zuydam, Natalie
AU - Cann, Jennifer A.
AU - Negri, Victor Augusti
AU - Tsafou, Kalliopi
AU - Liu, Zhi
AU - McCrae, Christopher
AU - Rees, D. Gareth
AU - England, Elizabeth
AU - Guscott, Molly A.
AU - Houslay, Kirsty
AU - McCormick, Dominique
AU - Freeman, Anna
AU - Schofield, Darren
AU - Freeman, Adrian
AU - Cohen, E. Suzanne
AU - Thwaites, Ryan S.
AU - Brohawn, Zach
AU - Platt, Adam
AU - Openshaw, Peter J.M.
AU - Semple, Malcolm G.
AU - Baillie, J. Kenneth
AU - Wilkinson, Tom
AU - ISARIC4C Investigators
PY - 2024
DA - December
TI - IL-33 is associated with alveolar dysfunction in patients with viral lower respiratory tract disease
JO - Mucosal Immunology
EP - 325
VL - 18
IS - 2
DO - https://doi.org/10.1016/j.mucimm.2024.12.001
AB - Interleukin (IL)-33 is released following tissue damage, causing airway inflammation and remodelling via reduced IL-33 (IL-33red)/serum stimulation-2 (ST2) and oxidised IL-33 (IL-33ox)/receptor for advanced glycation end products (RAGE)/epidermal growth factor receptor (EGFR) pathways. This study aimed to identify associations of IL-33 with clinical outcomes and pathological mechanisms during viral lower respiratory tract disease (LRTD). Ultra-sensitive immunoassays were developed to measure IL-33red, IL-33oxand IL-33/sST2 complexes in samples from patients hospitalised with COVID-19. Immunohistochemistry and multiomics were used to characterise lung samples. Elevated IL-33 in the airway and IL-33/sST2 complex in the circulation correlated with poor clinical outcomes (death, need for intensive care or mechanical ventilation). IL-33 was localised to airway epithelial and endothelial barriers, whereasIL1RL1was expressed on aerocytes, alveolar endothelial cells specialised for gaseous exchange. IL-33 increased expression of mediators of neutrophilic inflammation, immune cell infiltration, interferon signalling and coagulation in endothelial cell cultures. Endothelial IL-33 signatures were strongly related with signatures associated with viral LRTD. Increased IL-33 release following respiratory viral infections is associated with poor clinical outcomes and might contribute to alveolar dysfunction. Although this does not show a causal relationship with disease, these results provide a rationale to evaluate pathological roles for IL-33 in viral LRTD.
PB - Elsevier
UR - https://publichealthscotland.scot/id/220334
KW - Coronavirus (COVID-19)
ER