IL-33 is associated with alveolar dysfunction in patients with viral lower respiratory tract disease - Repository

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: https://doi.org/10.1016/j.mucimm.2024.12.001

Abstract

Interleukin (IL)-33 is released following tissue damage, causing airway inflammation and remodelling via reduced IL-33 (IL-33^red)/serum stimulation-2 (ST2) and oxidised IL-33 (IL-33^ox)/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-33^red, IL-33^ox and 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, whereas IL1RL1 was 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.

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http://creativecommons.org/licenses/by/4.0/

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Scott, I., van Zuydam, N., Cann, J., Negri, V., Tsafou, K., Liu, Z., McCrae, C., Rees, D., England, E., Guscott, M., Houslay, K., McCormick, D., Freeman, A., Schofield, D., Freeman, A., Cohen, E., Thwaites, R., Brohawn, Z., Platt, A., Openshaw, P., Semple, M., Baillie, J., Wilkinson, T. & ISARIC4C Investigators 2024, 'IL-33 is associated with alveolar dysfunction in patients with viral lower respiratory tract disease', Mucosal Immunology, 18(2), pp. 312-325. https://doi.org/10.1016/j.mucimm.2024.12.001

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DOI: https://doi.org/10.1016/j.mucimm.2024.12.001