ArticlePloS one2012
Elevation in body temperature to fever range enhances and prolongs subsequent responsiveness of macrophages to endotoxin challenge.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis.Critical care medicine · 2017Pooled it
- Core Warming of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study.Therapeutic hypothermia and temperature management · 2023Trial
- Trial
- Permissive versus restrictive temperature thresholds in critically ill children with fever and infection: a multicentre randomized clinical pilot trial.Critical care (London, England) · 2019Trial
- Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype.Journal of hepatology · 2013Trial
- Engineering the tumor immune landscape: Translating non-invasive physical stimulation into tumor-associated macrophage-targeted cancer immunotherapy.Bioengineering & translational medicine · 2026Review
- The poikilothermic hypothesis of sepsis.Critical care (London, England) · 2026Review
- Endotoxin tolerance enhances breast cancer aggressiveness and alters inflammatory marker expression in tumor and spleen of mice.Frontiers in immunology · 2026Article
- Heat stress induced testicular impairment is related to orchitis and complement activation in Rongchang boars.Journal of animal science and biotechnology · 2025Article
- Development of a self-assembling multimeric Bann-RBD fusion protein in Pichia pastoris as a potential COVID-19 vaccine candidate.Scientific reports · 2025Article
- What's cooking? The effect of temperature on the immune response.Frontiers in immunology · 2025Review
- Niacin mitigates heat stress-induced reduction in performance of Taihe black-boned silky fowl through modulation of gut microorganisms and short-chain fatty acids.Frontiers in veterinary science · 2025Article
- Elucidation of the antipyretic and anti-inflammatory effect of 8-Frontiers in pharmacology · 2025Article
- Cold-blooded vertebrate utilizes behavioral fever to alleviate T cell apoptosis and optimize antimicrobial immunity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration.Nature cardiovascular research · 2024Article
- Immunogenicity studies of recombinant RBD SARS-CoV-2 as a COVID-19 vaccine candidate produced inVaccine: X · 2024Article
- Fever-Range Hyperthermia Promotes Macrophage Polarization towards Regulatory Phenotype M2b.International journal of molecular sciences · 2023Article
- Cold Mechanical Isolation of Placental Macrophages as a Method to Limit Procedure-Induced Activation of Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Macrophages are often considered the sentries in innate immunity, sounding early immunological alarms, a function which speeds the response to infection. Compared to the large volume of studies on regulation of macrophage function by pathogens or cytokines, relatively little attention has been devoted to the role of physical parameters such as temperature. Given that temperature is elevated during fever, a long-recognized cardinal feature of inflammation, it is possible that macrophage function is responsive to thermal signals. To explore this idea, we used LPS to model an aseptic endotoxin-induced inflammatory response in BALB/c mice and found that raising mouse body temperature by mild external heat treatment significantly enhances subsequent LPS-induced release of TNF-α into the peritoneal fluid. It also reprograms macrophages, resulting in sustained subsequent responsiveness to LPS, i.e., this treatment reduces "endotoxin tolerance" in vitro and in vivo. At the molecular level, elevating body temperature of mice results in a increase in LPS-induced downstream signaling including enhanced phosphorylation of IKK and IκB, NF-κB nuclear translocation and binding to the TNF-α promoter in macrophages upon secondary stimulation. Mild heat treatment also induces expression of HSP70 and use of HSP70 inhibitors (KNK437 or Pifithrin-µ) largely abrogates the ability of the thermal treatment to enhance TNF-α, suggesting that the induction of HSP70 is important for mediation of thermal effects on macrophage function. Collectively, these results support the idea that there has been integration between the evolution of body temperature regulation and macrophage function that could help to explain the known survival benefits of fever in organisms following infection.
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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.