Modeling "Two-Hit" Severe Pneumonia in Mice: Pathological Characteristics and Mechanistic Studies
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Updated: May 6, 2026
A Non-invasive and Technically Non-intensive Method for Induction and Phenotyping of Experimental Bacterial Pneumonia in Mice
Published on: September 28, 2016
Mengjia Zhao1, Bixu Wang2, Fangmei Zhou1
1School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Abstract:
Severe pneumonia is one of the most common critical diseases in clinical practice. Existing models for severe pneumonia have limitations, leading to limited clinical translation. In this study, a two-hit severe pneumonia mouse model was established by inducing primary pneumonia through intratracheal instillation of 800 μg lipopolysaccharide (LPS), followed by intraperitoneal injection of 10 mg/kg LPS. The effectiveness of various inflammatory indicators and the lung tissue damage during the time course of this model were confirmed and evaluated. At 3 h post two-hit, the IL-6, TNF-α levels in peripheral blood and bronchoalveolar lavage fluid (BALF), and the white blood cells, neutrophils, and lymphocytes in BALF notably exhibited the most pronounced elevation. At 12 h post two-hit, the white blood cells and neutrophils in peripheral blood significantly increased, accompanied by notable alterations in splenic immune cells and worsened pulmonary histopathological damage. Transcriptomics of lung tissue, microbiota analysis of lung and gut, as well as plasma metabolomics analyses further indicated changes in transcriptional profiles, microbial composition, and metabolites due to the two-hit modeling. These results validate that the two-hit model mimics the clinical presentation of severe pneumonia and serves as a robust experimental tool for studying the pathogenesis of severe pneumonia and developing and assessing treatment strategies.
Insights
A novel two-hit mouse model effectively replicates severe pneumonia, showing significant inflammatory and tissue damage. This robust model aids in studying severe pneumonia pathogenesis and evaluating new treatments.
Area of Science:
- * Pulmonary Medicine
- * Immunology
- * Microbiology
- * Metabolomics
Background:
- * Severe pneumonia is a critical illness with limited clinical translation due to existing model deficiencies.
- * Developing accurate experimental models is crucial for understanding severe pneumonia's complex mechanisms.
Purpose of the Study:
- * To establish and validate a "two-hit" mouse model for severe pneumonia.
- * To assess the model's ability to mimic clinical presentations and pathological changes.
- * To evaluate its utility as a tool for therapeutic development.
Main Methods:
- * Induction of primary pneumonia via intratracheal lipopolysaccharide (LPS) instillation, followed by intraperitoneal LPS injection.
- * Evaluation of inflammatory indicators (IL-6, TNF-α, white blood cells, neutrophils, lymphocytes) in blood and bronchoalveolar lavage fluid (BALF).
- * Analysis of splenic immune cell alterations, pulmonary histopathology, lung and gut microbiota, plasma metabolomics, and lung tissue transcriptomics.
Main Results:
- * Significant elevation of inflammatory markers and immune cells in BALF at 3 hours post-induction.
- * Increased peripheral white blood cells and neutrophils, altered splenic immune cells, and worsened lung damage at 12 hours.
- * Distinct changes in transcriptional profiles, microbial composition, and metabolites observed through multi-omics analyses.
Conclusions:
- * The "two-hit" model successfully mimics the clinical and pathological features of severe pneumonia.
- * This validated model serves as a powerful experimental tool for investigating severe pneumonia pathogenesis.
- * It provides a foundation for developing and assessing novel treatment strategies for severe pneumonia.
