Acute Pulmonary Inflammation
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The Acute Respiratory Distress Syndrome (ARDS) associated with COVID-19 caused by the SARS-CoV-2 virus represents the current greatest unmet medical need of a pulmonary inflammation condition.
In addition, airway diseases such as chronic pulmonary inflammation (including chronic obstructive pulmonary disease and asthma) exact an ever-increasing toll on human health as the population ages and environmental pollutants (including tobacco smoke) damage lung tissue of young and old alike. These conditions are induced and exacerbated by pro-inflammatory molecules keyed to respond to acute infection, but often result in chronic immunological responses that induce acute crises and damage lung tissue over time.
An important goal in pharmaceutics is to break the inflammatory cascade by blockage or suppression of specific cytokines and chemokines known to induce and amplify lung inflammation. Two such proteins, monocyte chemoattractant protein (MCP-1), and tumor necrosis factor alpha (TNF-α), are found to be associated with early and chronic infection and inflammation in humans, and are mirrored in rodent models of airway inflammation including the mouse LPS pulmonary inflammation model described below.
Intranasal administration of lipopolysaccharide (LPS), a bacterial endotoxin, has been shown to initiate a pro-inflammatory response in the lungs of mice. This LPS model recapitulates aspects of the inflammatory cascades that are associated with pulmonary inflammation associated with lung disease in humans, and so is useful as a screen for compounds that may disrupt these cascades and attenuate or abort the disease process.
In this study, we used steroidal anti-inflammatory Dexamethasone to pharmacologically validate this model of MCP-1 induction in mice four hours after LPS pulmonary challenge.
Dexamethasone was able to significantly reduce the levels of MCP-1 in lung tissue four hours after LPS challenge. This LPS model stands as a good predictor of pulmonary anti-inflammatory compounds. As a screen, it can point the way for further studies of promising compounds, in viewing relative levels of cytokine MCP-1.