Molecular Dynamics of Lipopolysaccharide-Induced Lung Injury in Rodents

Abstract

Acute respiratory distress syndrome (ARDS) is a common disease entity in critical care medicine and is still associated with a high mortality. Because of the heterogeneous character of ARDS, animal models are an insturment to study pathology in relatively standardized conditions. Rodent models can bridge the gap from in vitro investigations to large animal and clinical trials by facilitating large sample sizes under physiological conditions at comparatively low costs. One of the most commonly used rodent models of acute lung inflammation and ARDS is administration of lipopolysaccharide (LPS), either into the airways (direct, pulmonary insult) or systemically (indirect, extra-pulmonary insult). This narrative review discusses the dynamics of important pathophysiological pathways contributing to the physiological response to LPS-induced injury. Pathophysiological pathways of LPS-induced lung injury are not only influenced by the type of the primary insult (e.g., pulmonary or extra-pulmonary) and presence of additional stimuli (e.g., mechanical ventilation), but also by time. As such, findings in animal models of LPS-induced lung injury may depend on the time point at which samples are obtained and physiological data are captured. This review summarizes the current evidence and highlights uncertainties on the molecular dynamics of LPS-induced lung injury in rodent models, encouraging researchers to take accurate timing of LPS-induced injury into account when designing experimental trials.

Dual Effect of Soloxolone Methyl on LPS-Induced Inflammation In Vitro and In Vivo

“…Currently, there are many in vivo models of LPS-induced inflammation, including endotoxemia [ 28 , 29 ], acute injury of the lungs [ 30 , 31 ], kidneys [ 32 , 33 ], and liver [ 34 , 35 ], neuroinflammation, and neurodegeneration [ 36 , 37 ]. The basis of all these models is a massive and sharp increase in the level of pro-inflammatory cytokines in the blood serum (septic shock) [ 38 , 39 ], which then causes damage to internal organs with multiple organ failure [ 40 , 41 ] and organ fibrosis as a result [ 37 , 42 ].…”

“…The severity of the manifestations of LPS-induced inflammation depends on the dose of LPS and the route of administration (intravenous, intraperitoneal, intramuscular, intranasal, etc.) [ 30 ]. The administration of high LPS doses leads to the death of the animal, whereas the administration of low doses leads to the development of multiple organ injury [ 43 ].…”

LincRNA-Cox2 functions to regulate inflammation in alveolar macrophages during acute lung injury

“…While we identify lincRNA-Cox2 as a crucial element for maintaining lung homeostasis, we next performed LPS induced acute lung injury (ALI) to assess the importance of lincRNA-Cox2 during active inflammation. Using a 24 h time point, which shows the maximum influx of PMNs and cytokine/chemokine expression (Domscheit et al, 2020), we find that loss of lincRNA-Cox2 leads a decrease in neutrophil recruitment and altered cytokine/chemokine expression in both the BAL and serum (Figure 2). In acute lung injury, neutrophils are crucial for bacterial clearance during live infection, repair and tissue remodeling after ALI (Blázquez-Prieto et al, 2018;Giacalone et al, 2020).…”

Intranasal versus intratracheal exposure to lipopolysaccharides in a murine model of acute respiratory distress syndrome

“…On day two, all the outcomes were collected. We assessed the outcomes 24 h after exposure because it corresponds to the time at which the peak influx of neutrophils in the lung is observed in this model 43 . It is also recommended that maximal lung injury should be evident within 24 h of exposure to the inciting stimulus in animal models of ARDS 9 .…”