ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Double blockade of CD14 and complement C5 abolishes the cytokine storm and improves morbidity and survival in polymicrobial sepsis in mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- 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
- Inhibition of the complement component C5 and the Toll-like receptor molecule CD14 prevents systemic and local kidney inflammation in mice experiencing brain death.Scientific reports · 2025Article
- Monocyte human leukocyte antigen-DR-mediated diabetic nephropathy progression is a promising therapeutic target.Frontiers in endocrinology · 2025Article
- Protective effect of gut microbiota restored by fecal microbiota transplantation in a sepsis model in juvenile mice.Frontiers in immunology · 2024Article
- Pulmonary miRNA expression after polytrauma depends on the surgical invasiveness and displays an anti-inflammatory pattern by the combined inhibition of C5 and CD14.Frontiers in immunology · 2024Article
- Dual inhibition of complement C5 and CD14 attenuates inflammation in a cord blood model.Pediatric research · 2023Article
- 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
- Recurrent Respiratory Syncytial Virus Infection in a CD14-Deficient Patient.The Journal of infectious diseases · 2022Article
- Simultaneous C5 and CD14 inhibition limits inflammation and organ dysfunction in pig polytrauma.Frontiers in immunology · 2022Article
- Emerging therapeutic targets for sepsis.Expert opinion on therapeutic targets · 2021Review
- 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
- COVID-19: A collision of complement, coagulation and inflammatory pathways.Journal of thrombosis and haemostasis : JTH · 2020Review
- Mechanisms of haemolysis-induced kidney injury.Nature reviews. Nephrology · 2019Review
- Clinical promise of next-generation complement therapeutics.Nature reviews. Drug discovery · 2019Review
- Dual inhibition of complement factor 5 and leukotriene B4 synergistically suppresses murine pemphigoid disease.JCI insight · 2019Article
- Tolerizing CTL by Sustained Hepatic PD-L1 Expression Provides a New Therapy Approach in Mouse Sepsis.Theranostics · 2019Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis and septic shock, caused by an excessive systemic host-inflammatory response, are associated with high morbidity and mortality. The complement system and TLRs provide important pattern recognition receptors initiating the cytokine storm by extensive cross-talk. We hypothesized that double blockade of complement C5 and the TLR coreceptor CD14 could improve survival of experimental polymicrobial sepsis. Mice undergoing cecal ligation and puncture (CLP)-induced sepsis were treated with neutralizing anti-CD14 Ab biG 53, complement C5 inhibitor coversin (Ornithodoros moubata C inhibitor), or a combination thereof. The inflammatory study (24-h observation) revealed statistically significant increases in 22 of 24 measured plasma biomarkers in the untreated CLP group, comprising 14 pro- and anti-inflammatory cytokines and 8 chemokines, growth factors, and granulocyte activation markers. Single CD14 or C5 blockade significantly inhibited 20 and 19 of the 22 biomarkers, respectively. Combined CD14 and C5 inhibition significantly reduced all 22 biomarkers (mean reduction 85%; range 54-95%) compared with the untreated CLP group. Double blockade was more potent than single treatment and was required to significantly inhibit IL-6 and CXCL1. Combined inhibition significantly reduced morbidity (motility and eyelid movement) and mortality measured over 10 d. In the positive control CLP group, median survival was 36 h (range 24-48 h). Combined treatment increased median survival to 96 h (range 24-240 h) (p = 0.001), whereas survival in the single-treatment groups was not significantly increased (median and range for anti-CD14 and anti-C5 treatment were 36 h [24-48 h] and 48 h [24-96 h]). Combined with standard intervention therapy, specific blockade of CD14 and C5 might represent a promising new therapeutic strategy for treatment of polymicrobial sepsis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.