ArticleShock (Augusta, Ga.)2020
Monophosphoryl Lipid a Attenuates Multiorgan Dysfunction During Post-Burn Pseudomonas Aeruginosa Pneumonia in Sheep.
Article in Shock (Augusta, Ga.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Tissue context as a determinant of trained innate immunity: a conserved molecular toolkit with divergent functional outputs.Journal of leukocyte biology · 2026Review
- Modeling Sepsis: Establishment and Validation of a 72-Hour Swine Model of Penetrating Abdominal Trauma.Medicina (Kaunas, Lithuania) · 2025Article
- Efficacy and clinical potential of phage therapy in treating methicillin-resistant Staphylococcus aureus (MRSA) infections: A review.European journal of microbiology & immunology · 2024Review
- Effects of maternal ritodrine hydrochloride administration on the heart rate of preterm fetal sheep with intraamniotic inflammation.PloS one · 2022Article
- Article
- Modulation of oxidative and nitrosative stress attenuates microvascular hyperpermeability in ovine model of Pseudomonas aeruginosa sepsis.Scientific reports · 2021Article
- Burns and biofilms: priority pathogens and in vivo models.NPJ biofilms and microbiomes · 2021Review
- TLR Agonists as Mediators of Trained Immunity: Mechanistic Insight and Immunotherapeutic Potential to Combat Infection.Frontiers in immunology · 2020Review
- Immunobiology and application of toll-like receptor 4 agonists to augment host resistance to infection.Pharmacological research · 2019Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMonophosphoryl lipid A (MPLA) is a TLR4 agonist that has potent immunomodulatory properties and modulates innate immune function to improve host resistance to infection with common nosocomial pathogens in mice. The goal of this study was to assess the safety and efficacy of MPLA in a sheep model of burn injury and Pseudomonas aeruginosa pneumonia. The sheep provides a favorable model for preclinical testing as their response to TLR4 agonists closely mimics that of humans.
methodsTwelve chronically instrumented adult female Merino sheep received 20% total body surface area, third-degree cutaneous burn under anesthesia and analgesia. At 24 h after burn, sheep were randomly allocated to receive: MPLA (2.5 μg/kg i.v., n = 6), or vehicle (i.v., n = 6). At 24 h after MPLA or vehicle treatment, Pseudomonas aeruginosa pneumonia was induced. Sheep were mechanically ventilated, fluid resuscitated and cardiopulmonary variables were monitored for 24 h after induction of pneumonia. Cytokine production, vascular barrier function, and lung bacterial burden were also measured.
resultsMPLA infusion induced small and transient alterations in core body temperature, heart rate, pulmonary artery pressure, and pulmonary vascular resistance. Pulmonary mechanics were not altered. Vehicle-treated sheep developed severe acute lung injury during Pseudomonas aeruginosa pneumonia, which was attenuated by MPLA as indicated by improved PaO2/FiO2 ratio, oxygenation index, and shunt fraction. Sheep treated with MPLA also exhibited less vascular leak, lower blood lactate levels, and lower modified organ injury score. MPLA treatment attenuated systemic cytokine production and decreased lung bacterial burden.
conclusionsMPLA was well tolerated in burned sheep and attenuated development of acute lung injury, lactatemia, cytokinemia, vascular leak, and hemodynamic changes caused by Pseudomonas aeruginosa pneumonia.
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Registered trials
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