ArticleJCI insight2018
Haptoglobin improves shock, lung injury, and survival in canine pneumonia.
Article in JCI insight, 2018. 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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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.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Heme-mediated selection of encapsulatedEmerging microbes & infections · 2025Article
- Hemolysis and Its Clinical Implications in Septic Patients with Acute Respiratory Failure.Journal of clinical medicine · 2025Article
- Elevated cell-free hemoglobin: A novel early biomarker following traumatic injury.The journal of trauma and acute care surgery · 2025Article
- Cardiopulmonary bypass with deep hypothermic circulatory arrest results in organ-specific transcriptomic responses in pediatric swine.Translational research : the journal of laboratory and clinical medicine · 2025Article
- Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study.Nature communications · 2025Observational
- Signs of Hemolysis Predict Mortality and Ventilator Associated Pneumonia in Severe Acute Respiratory Distress Syndrome Patients Undergoing Veno-Venous Extracorporeal Membrane Oxygenation.ASAIO journal (American Society for Artificial Internal Organs : 1992) · 2025Article
- Significant alterations in peripheral lymphocyte subsets and immune-related protein profiles in patients with periprosthetic joint infection.Frontiers in immunology · 2025Article
- Cell-Free Hemoglobin in the Pathophysiology of Trauma: A Scoping Review.Critical care explorations · 2024Article
- Moderate exercise-induced dynamics on key sepsis-associated signaling pathways in the liver.Critical care (London, England) · 2023Article
- Potential of cell-free hemoglobin and haptoglobin as prognostic markers in patients with ARDS and treatment with veno-venous ECMO.Journal of intensive care · 2023Article
- Large Animal Models for Simulating Physiology of Transfusion of Red Cell Concentrates-A Scoping Review of The Literature.Medicina (Kaunas, Lithuania) · 2022Article
- High-mobility group box 1 (HMGB1) in COVID-19: extrapolation of dangerous liaisons.Inflammopharmacology · 2022Review
- Higher serum haptoglobin levels were associated with improved outcomes of patients with septic shock.Critical care (London, England) · 2022Article
- Toxic effects of cell-free hemoglobin on the microvascular endothelium: implications for pulmonary and nonpulmonary organ dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Mechanistic insights into cell-free hemoglobin-induced injury during septic shock.American journal of physiology. Heart and circulatory physiology · 2021Article
- Haptoglobin treatment prevents cell-free hemoglobin exacerbated mortality in experimental rat sepsis.Intensive care medicine experimental · 2021Article
- Emerging pharmacological therapies for ARDS: COVID-19 and beyond.Intensive care medicine · 2020Article
- Marked Increased Production of Acute Phase Reactants by Skeletal Muscle during Cancer Cachexia.Cancers · 2020Article
- Expression profiles of genes associated with inflammatory responses and oxidative stress in lung after heat stroke.Bioscience reports · 2020Article
- Iron overload causes a mild and transient increase in acute lung injury.Physiological reports · 2020Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
During the last half-century, numerous antiinflammatory agents were tested in dozens of clinical trials and have proven ineffective for treating septic shock. The observation in multiple studies that cell-free hemoglobin (CFH) levels are elevated during clinical sepsis and that the degree of increase correlates with higher mortality suggests an alternative approach. Human haptoglobin binds CFH with high affinity and, therefore, can potentially reduce iron availability and oxidative activity. CFH levels are elevated over approximately 24-48 hours in our antibiotic-treated canine model of S. aureus pneumonia that simulates the cardiovascular abnormalities of human septic shock. In this 96-hour model, resuscitative treatments, mechanical ventilation, sedation, and continuous care are translatable to management in human intensive care units. We found, in this S. aureus pneumonia model inducing septic shock, that commercial human haptoglobin concentrate infusions over 48-hours bind canine CFH, increase CFH clearance, and lower circulating iron. Over the 96-hour study, this treatment was associated with an improved metabolic profile (pH, lactate), less lung injury, reversal of shock, and increased survival. Haptoglobin binding compartmentalized CFH to the intravascular space. This observation, in combination with increasing CFHs clearance, reduced available iron as a potential source of bacterial nutrition while decreasing the ability for CFH and iron to cause extravascular oxidative tissue injury. In contrast, haptoglobin therapy had no measurable antiinflammatory effect on elevations in proinflammatory C-reactive protein and cytokine levels. Haptoglobin therapy enhances normal host defense mechanisms in contrast to previously studied antiinflammatory sepsis therapies, making it a biologically plausible novel approach to treat septic shock.
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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.