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MD Biosciences Blog

LPS-induced Lung Injury and Fibrosis Models for COVID-19 Therapeutic Developments

Posted by MD Biosciences

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on Sep 29, 2020 3:51:28 PM

Most severe COVID-19 patients develop pneumonia and hyper-inflammation, likely
related to a macrophage activation syndrome commonly named “cytokine storm”.
The overproduction of early response pro-inflammatory cytokines (tumor necrosis
factor [TNF], IL-6, and IL-1β) results in an increased risk of vascular hyper-permeability,
multi-organ failure, and eventually death, when the high cytokine concentrations are unabated over time.
The pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2)-induced acute respiratory distress syndrome (ARDS) has similarities to that
of severe community-acquired pneumonia caused by other viruses or bacteria. LPS
induced ARDS is widely used to study host-response patterns in the pulmonary
The LPS lung inflammation model is an acute lung inflammation model where researchers can observe the pulmonary response following exposure to bacteria. Following induction by the oral aspiration of LPS, leukocytes are recruited into the lung cavity and parenchyma. Therefore, using this model, it is possible to measure and characterize the cellular profile of recruited leukocytes to the lung airways as well as the levels of pro-inflammatory cytokines.
Linked to the inflammatory response, lung fibrosis emerges as a secondary event
related to the progression of the pathology. Understanding the link between the
hyper-inflammation phase and fibrosis will give rise to new therapeutic targets
especially beneficial in the most severe cases of COVID-19. Our bleomycin-induced
fibrosis model accurately mimics this process. With one single dose of bleomycin, there is the onset of an acute inflammatory response, followed by fibrogenic changes, resulting in deposition of matrix and distortion of lung structure. The bleomycin model of pulmonary fibrosis is very helpful to illustrate pathobiology in vivo and to identify new targets for medication. It is an extremely beneficial tool to assess efficacy of potential compounds in general as proof of principle. 

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Topics: preclinical research, COVID-19