LPS-induced Pulmonary Neutrophilia Model

Models of acute pulmonary neutrophilia in response to lipopolysaccharide (LPS) challenge can be used to investigate the effect of targeting mechanisms related to neutrophil recruitment and mediator release, which are pertinent to diseases such as adult respiratory distress syndrome (ARDS), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).

Mouse Model:  By exposing mice to an airway challenge of lipopolysaccharide (LPS) via the intranasal route, a marked neutrophilia in the bronchoalveolar lavage (BAL) fluid is induced, which attains statistical significance within 4 hours and then remains elevated for over 24 hours. There are also increases in inflammatory mediators (e.g., TNF) in the BAL fluid, which reaches a maximal level 2 hours after LPS challenge. The inflammation is sensitive to steroids, both oral and inhaled.

Rat Model: LPS can be administered via the intratracheal route or via aqueous aerosol. This induces a marked neutrophilia in the BALF, which attains statistical significance within 4 hours and remains elevated for over 24 hours. The increases in BALF neutrophil numbers are robust and reproducible across multiple studies. There are also increases in inflammatory mediators (e.g., TNF) in the BAL fluid. The inflammation is sensitive to steroids (both oral and inhaled) and other anti-inflammatory agents, such as PDE4 inhibitors.

Guinea Pig Model: LPS can be administered via the intratracheal route or via aqueous aerosol. This induces a marked neutrophilia in the BAL fluid, which attains statistical significance within 4 hours and remains elevated for over 24 hours. The inflammation is sensitive to steroids.

To compare the activity of compounds or mechanisms of interest in the lungs versus the systemic compartment, models of systemic inflammation in response to LPS challenge have been established in the rat and mouse.

Induced by administering LPS via the intravenous route, the model has been established with time courses and dose-response curves to LPS showing reproducible increases in inflammatory mediators (e.g., TNF) in the blood, which are reduced by pre-dosing with steroids.

Additional services that can be combined with this model include inflammatory mediator profiling and histopathologic evaluations.

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