ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
Elevated CO2 selectively inhibits interleukin-6 and tumor necrosis factor expression and decreases phagocytosis in the macrophage.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- What is the evidence for the use of low-pressure pneumoperitoneum? A systematic review.Surgical endoscopy · 2016Pooled it
- Hypercapnia enhances airway smooth muscle contractility via STIM1-dependent Ca2+ signaling.JCI insight · 2026Article
- Effects of Permissive Hypercapnia During Lung Surgery on Inflammatory Biomarkers in Serum and Bronchoalveolar Lavage Fluid: A Randomized Controlled Trial.Metabolites · 2026Article
- Molecular and Cellular Signaling Pathways of the Effects of Hypoxia and Hypercapnia on the Mechanisms of Neuroinflammation.International journal of molecular sciences · 2026Review
- Therapeutic Gases in Biomedicine: Updates on Nitric Oxide and Beyond.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Hypercapnia Effects on Lung Function.Comprehensive Physiology · 2026Review
- The Association Between the Eosinophilic COPD Phenotype with Overall Survival and Exacerbations in Patients on Long-Term Non-Invasive Ventilation.Biomolecules · 2025Article
- Comparative transcriptomic and meat quality responses to electrical and controlled atmosphere stunning in broiler chickens.Poultry science · 2025Article
- Hypercapnia as a Double-Edged Modulator of Innate Immunity and Alveolar Epithelial Repair: A PRISMA-ScR Scoping Review.International journal of molecular sciences · 2025Article
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- The new perspective on understanding the mechanisms of cardiovascular diseases development.Scientific reports · 2025Article
- Therapeutic Potential ofInternational journal of molecular sciences · 2025Article
- Hypercapnic acidosis affectsFrontiers in cellular and infection microbiology · 2025Article
- Influence of the spaceflight environment on macrophage lineages.NPJ microgravity · 2024Review
- Unveiling cytokine charge disparity as a potential mechanism for immune regulation.Cytokine & growth factor reviews · 2024Review
- Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.JCI insight · 2024Article
- Microglial reactivity in brainstem chemosensory nuclei in response to hypercapnia.Frontiers in physiology · 2024Article
- Lowering PRespiratory care · 2023Article
- Mild and moderate chronic hypercapnia elicit distinct transcriptomic responses of immune function in cardiorespiratory nuclei.Physiological genomics · 2023Article
- Carbon dioxide and MAPK signalling: towards therapy for inflammation.Cell communication and signaling : CCS · 2023Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Elevated blood and tissue CO(2), or hypercapnia, is common in severe lung disease. Patients with hypercapnia often develop lung infections and have an increased risk of death following pneumonia. To explore whether hypercapnia interferes with host defense, we studied the effects of elevated P(CO2) on macrophage innate immune responses. In differentiated human THP-1 macrophages and human and mouse alveolar macrophages stimulated with lipopolysaccharide (LPS) and other Toll-like receptor ligands, hypercapnia inhibited expression of tumor necrosis factor and interleukin (IL)-6, nuclear factor (NF)-kappaB-dependent cytokines critical for antimicrobial host defense. Inhibition of IL-6 expression by hypercapnia was concentration dependent, rapid, reversible, and independent of extracellular and intracellular acidosis. In contrast, hypercapnia did not down-regulate IL-10 or interferon-beta, which do not require NF-kappaB. Notably, hypercapnia did not affect LPS-induced degradation of IkappaB alpha, nuclear translocation of RelA/p65, or activation of mitogen-activated protein kinases, but it did block IL-6 promoter-driven luciferase activity in mouse RAW 264.7 macrophages. Elevated P(CO2) also decreased phagocytosis of opsonized polystyrene beads and heat-killed bacteria in THP-1 and human alveolar macrophages. By interfering with essential innate immune functions in the macrophage, hypercapnia may cause a previously unrecognized defect in resistance to pulmonary infection in patients with advanced lung disease.
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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.