In Vivo Model Development for Acute Lung Injury

Protheragen offers a comprehensive in vivo animal model development service for Acute Lung Injury (ALI), supporting drug discovery and translational research. Our service leverages a wide array of well-characterized animal models—spanning multiple species, strains, and induction methods—to provide robust platforms for evaluating the efficacy and safety of novel therapeutics targeting ALI and related pulmonary disorders.

Acute Lung Injury (ALI) and its more severe form, Acute Respiratory Distress Syndrome (ARDS), represent critical clinical challenges with significant morbidity and mortality. Animal models are indispensable tools for unraveling the complex pathophysiology of ALI, identifying therapeutic targets, and assessing candidate interventions prior to clinical trials. At Protheragen, we employ a diverse selection of species—including mice (Mus musculus), rats (Rattus norvegicus), minipigs (Gottingen), cynomolgus monkeys (Macaca fascicularis), and domestic pigs (Sus scrofa)—and a variety of strains such as C57BL/6, Balb/c, CD-1, Swiss, Sprague Dawley, and Wistar. This diversity enables modeling of disease mechanisms that closely parallel human ALI, ensuring translational relevance and scientific rigor in preclinical studies.

Chemically-Induced Models

Chemically-induced ALI models involve the administration of agents such as bleomycin sulfate, paraquat, oleic acid, human neutrophil elastase, silicon dioxide, sulfur mustard, hydrochloric acid, and others directly to the respiratory system or systemically. These agents provoke acute lung injury through oxidative stress, inflammation, alveolar-capillary barrier disruption, and fibrosis. The methodology typically includes intratracheal, intravenous, or intraperitoneal delivery, with subsequent monitoring of lung pathology. Key advantages of chemically-induced models are their reproducibility, dose-dependent response, and ability to mimic specific aspects of human ALI, such as interstitial fibrosis or alveolar damage. They are widely used for mechanistic studies, compound screening, and evaluation of anti-inflammatory or anti-fibrotic therapies.

Biologically-Induced Models

Biologically-induced ALI models utilize agents such as lipopolysaccharide (LPS), live bacteria, or viral pathogens to trigger an inflammatory response in the lungs. LPS, a component of Gram-negative bacterial cell walls, is commonly delivered intratracheally or intraperitoneally to induce robust neutrophilic inflammation, cytokine release, and pulmonary edema. Bacterial and viral infection models employ clinically relevant pathogens to recapitulate infectious ALI, while antibody-induced models (e.g., anti-MHC class I) simulate immune-mediated injury. The main advantages are the close resemblance to clinical scenarios of sepsis or pneumonia-induced ALI, and the opportunity to study immune mechanisms and host-pathogen interactions. These models are ideal for evaluating antimicrobial, immunomodulatory, and supportive therapies.

Genetic and Transgenic Models

Genetic and transgenic ALI models involve the use of animals with specific gene knockouts, knock-ins, or transgenic modifications (e.g., ACE2 transgenic mice, Hmox1, Arf6, Npr3, Icam1, Itgb2, or C1qa knockouts). These models allow for the investigation of gene-specific contributions to ALI pathogenesis, susceptibility, and therapeutic response. Methodologies include breeding or engineering animals with targeted genetic alterations, followed by exposure to injurious stimuli such as LPS, mechanical ventilation, or infection. The advantages are the ability to dissect molecular pathways, validate drug targets, and explore gene-environment interactions. These models are essential for precision medicine research and for understanding the genetic basis of ALI.

Mechanical and Physical Injury Models

Mechanical and physical injury models induce ALI through interventions such as mechanical ventilation with high tidal volumes, traumatic brain injury, cecal ligature-puncture (to model sepsis), hyperoxia exposure, cardiopulmonary bypass, or hemorrhagic shock. These approaches mimic clinical risk factors and complications associated with ALI in critical care settings. The methodology involves controlled delivery of mechanical or physiological stressors, with subsequent assessment of lung function and injury. Advantages include high clinical relevance for ventilator-induced lung injury (VILI), trauma, or multi-organ dysfunction. These models are suitable for studying supportive care strategies, ventilator settings, and organ cross-talk in ALI.

Protheragen delivers a complete, end-to-end solution for in vivo ALI model development and testing. Our service encompasses model selection and customization, precise induction protocols, comprehensive monitoring, and advanced endpoint analysis. Key efficacy endpoints include survival, lung wet/dry weight ratio, bronchoalveolar lavage fluid (BALF) analysis (cell counts, cytokines, protein leakage), histopathology, arterial blood gas analysis, pulmonary function tests, and imaging (e.g., micro-CT). Analytical capabilities extend to molecular assays (qPCR, Western blot, ELISA), immunohistochemistry, and flow cytometry. Rigorous quality control measures are implemented at every stage, including standardized protocols, validated reagents, and strict animal welfare compliance, ensuring reproducible and high-quality data.

By partnering with Protheragen, you gain access to unmatched expertise in animal modeling for Acute Lung Injury, a broad spectrum of validated and customizable models, and a commitment to scientific excellence. Our integrated approach accelerates the translation of your therapeutic concepts from bench to bedside, while our dedicated team ensures timely delivery and regulatory support. Contact us today to discuss your ALI research needs and discover how Protheragen can advance your preclinical development program.