ArticleInfection and immunity2009
Inhibition of complement and CD14 attenuates the Escherichia coli-induced inflammatory response in porcine whole blood.
Article in Infection and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- An Unsettled Promise: The Newborn Piglet Model of Neonatal Acute Respiratory Distress Syndrome (NARDS). Physiologic Data and Systematic Review.Frontiers in physiology · 2019Pooled it
- Investigating the Antioxidant and Immunomodulatory Effects of Quercetin Using Porcine PBMCs as an Inflammatory In Vitro Model.Antioxidants (Basel, Switzerland) · 2026Article
- CD14 Blockade Does Not Improve Outcomes of Deep Vein Thrombosis Following Inferior Vena Cava Stenosis in Mice.bioRxiv : the preprint server for biology · 2024Article
- Dual inhibition of complement C5 and CD14 attenuates inflammation in a cord blood model.Pediatric research · 2023Article
- CD14 blockade to prevent ischemic injury to donor organs.Transplant immunology · 2022Review
- Monocyte upregulation of podoplanin during early sepsis induces complement inhibitor release to protect liver function.JCI insight · 2020Article
- IgM cleavage by Streptococcus suis reduces IgM bound to the bacterial surface and is a novel complement evasion mechanism.Virulence · 2018Article
- Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model ofProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Combined Inhibition of Complement and CD14 Attenuates Bacteria-Induced Inflammation in Human Whole Blood More Efficiently Than Antagonizing the Toll-like Receptor 4-MD2 Complex.The Journal of infectious diseases · 2016Article
- Human Endothelial Cell Activation by Escherichia coli and Staphylococcus aureus Is Mediated by TNF and IL-1β Secondarily to Activation of C5 and CD14 in Whole Blood.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention.European journal of clinical investigation · 2015Review
- Post challenge inhibition of C3 and CD14 attenuates Escherichia coli-induced inflammation in human whole blood.Innate immunity · 2014Article
- Chimeric anti-CD14 IGG2/4 Hybrid antibodies for therapeutic intervention in pig and human models of inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Systemic CD14 inhibition attenuates organ inflammation in porcine Escherichia coli sepsis.Infection and immunity · 2013Article
- CD14 directs adventitial macrophage precursor recruitment: role in early abdominal aortic aneurysm formation.Journal of the American Heart Association · 2013Article
- Immunogenomics for identification of disease resistance genes in pigs: a review focusing on Gram-negative bacilli.Journal of animal science and biotechnology · 2012Article
- Anti-inflammatory effects of C1-Inhibitor in porcine and human whole blood are independent of its protease inhibition activity.Innate immunity · 2010Article
- CD14 inhibition efficiently attenuates early inflammatory and hemostatic responses in Escherichia coli sepsis in pigs.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- Therapeutic potential of complement modulation.Nature reviews. Drug discovery · 2010Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
The innate immune response is a double-edged sword in systemic inflammation and sepsis. Uncontrolled or inappropriate activation can damage and be lethal to the host. Several studies have investigated inhibition of downstream mediators, including tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta). Emerging evidence indicates that upstream inhibition is a better therapeutic approach for attenuating damaging immune activation. Therefore, we investigated inhibition of two central innate immune pathways, those of complement and CD14/Toll-like receptor 4 (TLR4)/myeloid differentiation protein 2 (MD-2), in a porcine in vitro model of Escherichia coli-induced inflammation. Porcine whole blood anticoagulated with lepuridin, which did not interfere with the complement system, was incubated with E. coli lipopolysaccharide (LPS) or whole bacteria. Inhibitors of complement and CD14 and thus the LPS CD14/TLR4/MD-2 receptor complex were tested to investigate the effect on the inflammatory response. A broad range of inflammatory readouts were used to monitor the effect. Anti-CD14 was found to saturate the CD14 molecule on granulocytes and completely inhibited LPS-induced proinflammatory cytokines in a dose-dependent manner. Anti-CD14 significantly reduced the levels of the E. coli-induced proinflammatory cytokines TNF-alpha and IL-1beta, but not IL-8, in a dose-dependent manner. No effect on bacterial clearance was seen. Vaccinia complement control protein and smallpox inhibitor of complement enzymes, two Orthopoxvirus-encoded complement inhibitors, completely inhibited complement activation. Furthermore, these agents almost completely inhibited the expression of wCD11R3, which is associated with CD18 as a beta2 integrin, on porcine granulocytes and decreased IL-8 levels significantly in a dose-dependent manner. As expected, complement inhibition reduced bacterial clearance. We conclude that inhibition of complement and CD14 attenuates E. coli-induced inflammation and might be used as a therapeutic regimen in gram-negative sepsis along with appropriate treatment with antibiotics.
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Registered trials
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.