ArticleRespiratory research2018
GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.
Article in Respiratory research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04400929 (Using GM-CSF as a Host Directed Therapeutic Against COVID-19 - a Phase 2 Investigator Initiated Trial), which is not on this map. Cited by 51 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.
Using GM-CSF as a Host Directed Therapeutic Against COVID-19 - a Phase 2 Investigator Initiated Trial
Who cites it
51 citing papers in PubMed, 77 citations in OpenAlex.
- Lung microbiota dysbiosis exacerbates influenza virus infection.Microbiome · 2026Article
- Suppression of Nr1d1/Bnip3-dependent mitophagy by notch signaling aggravates inflammatory response in RSV-infected mice lungs.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Bioprinted Ventilated 3D Alveoliform Epithelial Sacculoids.Research square · 2025Article
- Chick early amniotic fluid attenuates lipopolysaccharide-induced acute lung injury.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- PROS1/AXL signaling protects mice from lethal influenza infection by inducing M2 macrophage polarization.Acta biochimica et biophysica Sinica · 2025Article
- B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine.Nature immunology · 2025Article
- Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.International journal of molecular sciences · 2025Review
- Viral sepsis: diagnosis, clinical features, pathogenesis, and clinical considerations.Military Medical Research · 2024Review
- Unraveling Macrophage Polarization: Functions, Mechanisms, and "Double-Edged Sword" Roles in Host Antiviral Immune Responses.International journal of molecular sciences · 2024Review
- Treatment with lipoxin AInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Treatment with lipoxin A 4 improves influenza A infection outcome through macrophage reprogramming, anti-inflammatory and pro-resolutive responses.Research square · 2024Article
- Pathogenicity and virulence of influenza.Virulence · 2023Review
- Alveolar Macrophages Participate in the Promotion of Influenza Virus Infection by Aflatoxin B1 at an Early Stage.Toxins · 2023Article
- RIG-I agonist SLR10 promotes macrophage M1 polarization during influenza virus infection.Frontiers in immunology · 2023Article
- Diverse roles of lung macrophages in the immune response to influenza A virus.Frontiers in microbiology · 2023Review
- Surfactant protein A alters endosomal trafficking of influenza A virus in macrophages.Frontiers in immunology · 2023Article
- Article
- From high-throughput to therapeutic: host-directed interventions against influenza viruses.Current opinion in virology · 2022Review
- Macrophages as a Therapeutic Target in Metastatic Prostate Cancer: A Way to Overcome Immunotherapy Resistance?Cancers · 2022Review
- Recombinant GM-CSF for diseases of GM-CSF insufficiency: Correcting dysfunctional mononuclear phagocyte disorders.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundInfluenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established.
methodsMice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi). Assessment of respiratory mechanical parameters was performed using the flexiVent rodent ventilator. RNA sequence analysis was performed on FACS-sorted airway macrophage subsets at 8 dpi.
resultsSupra-physiologic levels of GM-CSF conferred a survival benefit, arrested the deterioration of lung mechanics, and reduced the abundance of protein exudates in bronchoalveolar (BAL) fluid to near baseline levels. Transcriptome analysis, and subsequent validation ELISA assays, revealed that excess GM-CSF re-directs macrophages from an "M1-like" to a more "M2-like" activation state as revealed by alterations in the ratios of CXCL9 and CCL17 in BAL fluid, respectively. Ingenuity pathway analysis predicted that GM-CSF surplus during IAV infection elicits expression of anti-inflammatory mediators and moderates M1 macrophage pro-inflammatory signaling by Type II interferon (IFN-γ).
conclusionsOur data indicate that application of high levels of GM-CSF in the lung after influenza A virus infection alters pathogenic "M1-like" macrophage inflammation. These results indicate a possible therapeutic strategy for respiratory virus-associated pneumonia and acute lung injury.
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.