Lipopolysaccharide induces acute lung injury and alveolar haemorrhage in association with the cytokine storm, coagulopathy and AT1R/JAK/STAT augmentation in a rat model that mimics moderate and severe Covid‐19 pathology

• DOI: 10.1111/1440-1681.13620
• Publication Date: 2022-01-23T16:10:25Z
• Authors: Bahjat Al‐Ani; Asmaa M. ShamsEldeen; Samaa S. Kamar; Mohamed A. Haidara; Fahaid Al‐Hashem; Mohammad Y. Alsha...; Ahmed M. Al‐Hakami; Dina H. Abdel Kader; Amro Maarouf
• Keywords: Cytokine Storm

Progress in the study of Covid-19 disease rodents has been hampered by lack angiotensin-converting enzyme 2 (ACE2; virus entry route to target cell) affinities for spike proteins across species. Therefore, we sought determine whether a modified protocol lipopolysaccharide (LPS)-induced acute respiratory distress syndrome rats can mimic both cell signalling pathways as well severe phenotypes disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg LPS (model group) or saline (control before being killed after 3 days. A (SARS)-like effect was observed model group demonstrated development "cytokine storm" (>2.7 fold increase blood levels IL-6, IL-17A, GM-CSF, and TNF-α), high ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, APTT (p < 0.0001). In addition, increased expression lung angiotensin II type I receptor (AT1R)-JAK-STAT axis (>4 increase). Chest imaging revealed bilateral small patchy opacities lungs. Severe injury noted presence both, alveolar collapse haemorrhage, desquamation epithelial cells airway lumen, infiltration inflammatory (CD45+ leukocytes), widespread thickening interalveolar septa, ultrastructural alterations similar Covid-19. Thus, these findings demonstrate that IT injection into rats, induced an AT1R/JAK/STAT-mediated cytokine storm resultant pneumonia coagulopathy commensurate moderate humans.