ReviewJournal of leukocyte biology2017
Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases-C3 or C5 emerge together with CD14 as promising targets.
Review in Journal of leukocyte biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05062486 (An Open-Label, Randomized, Double Arm, Phase 2 Study to Evaluate the Safety and Efficacy of C and RQC for Preventing Progression in Age-Related Macular Degeneration), which is not on this map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-Label, Randomized, Double Arm, Phase 2 Study to Evaluate the Safety and Efficacy of C and RQC for Preventing Progression in Age-Related Macular Degeneration
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Loss of C3 and CD14 reduces region-specific neuroinflammation in a murine polytrauma model.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 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
- Lipid nanoparticle-mediated Cd14 siRNA delivery ameliorates the acute inflammatory response to intracortical microelectrode implantation.Acta biomaterialia · 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 activation during liver machine perfusion is shaped by perfusate composition and is independent of the ischemic injury.Frontiers in immunology · 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
- Extracellular mitochondrial DNA activates complement and is associated with complement activation in patients with out-of-hospital cardiac arrest.Scientific reports · 2025Article
- A novel long-acting C5a-blocking cyclic peptide prevents sepsis-induced organ dysfunction via effective blockade of the inflammatory cascade.Signal transduction and targeted therapy · 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
- Preparation, structural characteristics and immune regulatory effects ofFrontiers in immunology · 2025Review
- Clinical Value of Complement C3a, C5a, and sC5b-9 in Evaluating the Severity of Patients with Severe Fever with Thrombocytopenia Syndrome.Journal of inflammation research · 2025Article
- TLR2 and TLR4 Are Expressed in Epiretinal Membranes: Possible Links with Vitreous Levels of Complement Fragments and DAMP-Related Proteins.International journal of molecular sciences · 2024Article
- The Inflammatory Response Induced by Aspergillus fumigatus Conidia Is Dependent on Complement Activation: Insight from a Whole Blood Model.Journal of innate immunity · 2024Article
- Normothermic Machine Perfusion Reconstitutes Porcine Kidney Tissue Metabolism But Induces an Inflammatory Response, Which Is Reduced by Complement C5 Inhibition.Transplant international : official journal of the European Society for Organ Transplantation · 2024Article
- Modulation of the hepatic RANK-RANKL-OPG axis by combined C5 and CD14 inhibition in a long-term polytrauma model.Frontiers in immunology · 2024Article
- Dual inhibition of complement C5 and CD14 attenuates inflammation in a cord blood model.Pediatric research · 2023Article
- Oligosaccharides as Potential Therapeutics against Atherosclerosis.Molecules (Basel, Switzerland) · 2023Review
- Complosome - the intracellular complement system.Nature reviews. Nephrology · 2023Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The host is protected by pattern recognition systems, including complement and TLRs, which are closely cross-talking. If improperly activated, these systems might induce tissue damage and disease. Inhibition of single downstream proinflammatory cytokines, such as TNF, IL-1β, and IL-6, have failed in clinical sepsis trials, which might not be unexpected, given the substantial amounts of mediators involved in the pathogenesis of this condition. Instead, we have put forward a hypothesis of inhibition at the recognition phase by "dual blockade" of bottleneck molecules of complement and TLRs. By acting upstream and broadly, the dual blockade could be beneficial in conditions with improper or uncontrolled innate immune activation threatening the host. Key bottleneck molecules in these systems that could be targets for inhibition are the central complement molecules C3 and C5 and the important CD14 molecule, which is a coreceptor for several TLRs, including TLR4 and TLR2. This review summarizes current knowledge of inhibition of complement and TLRs alone and in combination, in both sterile and nonsterile inflammatory processes, where activation of these systems is of crucial importance for tissue damage and disease. Thus, dual blockade might provide a general, broad-acting therapeutic regimen against a number of diseases where innate immunity is improperly activated.
Indexed as
Identifiers
What OpenQuestion holds
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.