ReviewShock (Augusta, Ga.)2020
Complement as a Major Inducer of Harmful Events in Infectious Sepsis.
Review 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 27 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Early amyloid pathology in mice synergistically worsens post-sepsis behavioral impairment and microglial synaptic phagocytosis.Brain, behavior, & immunity - health · 2026Article
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Epigenetic Mechanisms in Sepsis-Induced Cardiomyopathy: From Pathophysiology to Therapeutic Targets.International journal of molecular sciences · 2026Review
- Integrative metabolite-protein interaction networks reveal potential pathways and biomarkers in sepsis.BMC infectious diseases · 2026Article
- The immunology of sepsis: translating new insights into clinical practice.Nature reviews. Nephrology · 2026Review
- 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
- The Crosstalk Between Sepsis-Associated Encephalopathy and Alzheimer's Disease: Identifying Potential Biomarkers and Therapeutic Targets for Cognition.Molecular neurobiology · 2025Article
- Deficiencies of carboxypeptidase N and carboxypeptidase B2 have opposite effects in a virulent mouse E. coli sepsis model.Journal of thrombosis and haemostasis : JTH · 2025Article
- Molecular Diplomacy of Lipids in the War of Immunity: Bridging Rare and Common Disease Mechanisms.International journal of molecular sciences · 2025Article
- Disseminated intravascular coagulation.Journal of intensive care · 2025Review
- Biomarkers as Beacons: Illuminating Sepsis-Associated Hepato-Renal Injury.International journal of molecular sciences · 2025Review
- Decoding Sepsis: Unraveling Key Signaling Pathways for Targeted Therapies.Research (Washington, D.C.) · 2025Review
- Complement activation and lung injury in Japanese patients with COVID-19: a prospective observational study.Scientific reports · 2024Observational
- C5a Induces Inflammatory Signaling and Apoptosis in PC12 Cells through C5aR-Dependent Signaling: A Potential Mechanism for Adrenal Damage in Sepsis.International journal of molecular sciences · 2024Article
- Protective effects of nordalbergin against LPS-induced endotoxemia through inhibiting MAPK/NF-κB signaling pathway, NLRP3 inflammasome activation, and ROS production.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Mononuclear phagocyte morphological response to chemoattractants is dependent on geranylgeranyl pyrophosphate.American journal of physiology. Endocrinology and metabolism · 2024Article
- Alpha1-antitrypsin improves survival in murine abdominal sepsis model by decreasing inflammation and sequestration of free heme.Frontiers in immunology · 2024Article
- C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps.The Journal of clinical investigation · 2023Article
- Treatment Advances in Sepsis and Septic Shock: Modulating Pro- and Anti-Inflammatory Mechanisms.Journal of clinical medicine · 2023Review
- Extracellular histone H3 facilitates ferroptosis in sepsis through ROS/JNK pathway.Immunity, inflammation and disease · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
There is abundant evidence that infectious sepsis both in humans and mice with polymicrobial sepsis results in robust activation of complement. Major complement activation products involved in sepsis include C5a anaphylatoxin and its receptors (C5aR1 and C5aR2) and, perhaps, the terminal complement activation product, C5b-9. These products (and others) also cause dysfunction of the innate immune system, with exaggerated early proinflammatory responses, followed by decline of the innate immune system, leading to immunosuppression and multiorgan dysfunction. Generation of C5a during sepsis also leads to activation of neutrophils and macrophages and ultimate appearance of extracellular histones, which have powerful proinflammatory and prothrombotic activities. The distal complement activation product, C5b-9, triggers intracellular Ca fluxes in epithelial and endothelial cells. Histones activate the NLRP3 inflammasome, products of which can damage cells. C5a also activates MAPKs and Akt signaling pathways in cardiomyocytes, causing buildup of [Ca]i, defective action potentials and substantial cell dysfunction, resulting in cardiac and other organ dysfunction. Cardiac dysfunction can be quantitated by ECHO-Doppler parameters. In vivo interventions that block these complement-dependent products responsible for organ dysfunction in sepsis reduce the intensity of sepsis. The obvious targets in sepsis are C5a and its receptors, histones, and perhaps the MAPK pathways. Blockade of C5 has been considered in sepsis, but the FDA-approved antibody (eculizumab) is known to compromise defenses against neisseria and pneumonococcal bacteria, and requires immunization before the mAb to C5 can be used clinically. Small molecular blocking agents for C5aRs are currently in development and may be therapeutically effective for treatment of sepsis.
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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.