ArticleCritical care (London, England)2015
Combined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsis.
Article in Critical care (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Anaesthesia for pigs, sheep, goats and cattle involved in biomedical research: FELASA working group guidelines-Parts I-IV.Laboratory animals · 2026Article
- Attenuating pulmonary injury and inflammation with C5/CD14 inhibition therapy: results from a porcine polytrauma model with blunt chest trauma.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2026Article
- Combined inhibition of the complement component C5 and the TLR-coreceptor CD14 alters the posttraumatic response in fracture hematoma in a porcine polytrauma model.Innovative surgical sciences · 2026Article
- Immune modulation mimics damage control orthopaedics' upregulation of anti-inflammatory miRNA-21/23a/27a and miRNA-30b in the lung after polytrauma in pigs.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025Article
- Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics.Cell death & disease · 2025Review
- Navigating the Modern Landscape of Sepsis: Advances in Diagnosis and Treatment.International journal of molecular sciences · 2024Review
- Modulation of the hepatic RANK-RANKL-OPG axis by combined C5 and CD14 inhibition in a long-term polytrauma model.Frontiers in immunology · 2024Article
- Targeting the host response in sepsis: current approaches and future evidence.Critical care (London, England) · 2023Review
- The complement system in pediatric acute kidney injury.Pediatric nephrology (Berlin, Germany) · 2023Review
- Immunopathology of terminal complement activation and complement C5 blockade creating a pro-survival and organ-protective phenotype in trauma.British journal of pharmacology · 2023Article
- Complement as a vital nexus of the pathobiological connectome for acute respiratory distress syndrome: An emerging therapeutic target.Frontiers in immunology · 2023Review
- Complement Activation in Patients With Heat-Related Illnesses: Soluble CD59 Is a Novel Biomarker Indicating Severity of Heat-Related Illnesses.Critical care explorations · 2022Article
- Venous Air Embolism Activates Complement C3 Without Corresponding C5 Activation and Trigger Thromboinflammation in Pigs.Frontiers in immunology · 2022Article
- Simultaneous C5 and CD14 inhibition limits inflammation and organ dysfunction in pig polytrauma.Frontiers in immunology · 2022Article
- CD14 inhibition improves survival and attenuates thrombo-inflammation and cardiopulmonary dysfunction in a baboon model of Escherichia coli sepsis.Journal of thrombosis and haemostasis : JTH · 2021Article
- Complement Inhibition and COVID-19: The Story so Far.ImmunoTargets and therapy · 2021Review
- High Mobility Group Box 1 and TLR4 Signaling Pathway in Gnotobiotic Piglets Colonized/Infected withInternational journal of molecular sciences · 2019Article
- Dual inhibition of complement factor 5 and leukotriene B4 synergistically suppresses murine pemphigoid disease.JCI insight · 2019Article
- Targeting Complement Pathways in Polytrauma- and Sepsis-Induced Multiple-Organ Dysfunction.Frontiers in immunology · 2019Review
- Selective and marked decrease of complement receptor C5aR2 in human thoracic aortic aneurysms: a dysregulation with potential inflammatory effects.Open heart · 2019Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionSepsis is an exaggerated and dysfunctional immune response to infection. Activation of innate immunity recognition systems including complement and the Toll-like receptor family initiate this disproportionate inflammatory response. The aim of this study was to explore the effect of combined inhibition of the complement component C5 and the Toll-like receptor co-factor CD14 on survival, hemodynamic parameters and systemic inflammation including complement activation in a clinically relevant porcine model of polymicrobial sepsis.
methodsNorwegian landrace piglets (4 ± 0.5 kg) were blindly randomized to a treatment group (n = 12) receiving the C5 inhibitor coversin (OmCI) and anti-CD14 or to a positive control group (n = 12) receiving saline. Under anesthesia, sepsis was induced by a 2 cm cecal incision and the piglets were monitored in standard intensive care for 8 hours. Three sham piglets had a laparotomy without cecal incision or treatment. Complement activation was measured as sC5b-9 using enzyme immunoassay. Cytokines were measured with multiplex technology.
resultsCombined C5 and CD14 inhibition significantly improved survival (p = 0.03). Nine piglets survived in the treatment group and four in the control group. The treatment group had significantly lower pulmonary artery pressure (p = 0.04) and ratio of pulmonary artery pressure to systemic artery pressure (p < 0.001). Plasma sC5b-9 levels were significantly lower in the treatment group (p < 0.001) and correlated significantly with mortality (p = 0.006). IL-8 and IL-10 were significantly (p < 0.05) lower in the treatment group.
conclusionsCombined inhibition of C5 and CD14 significantly improved survival, hemodynamic parameters and inflammation in a blinded, randomized trial of porcine polymicrobial sepsis.
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