| Title: | The role of interleukin-6 signalling in pleural infection: observational and genetic analyses |
| Journal: | EBioMedicine |
| Published: | 16 Aug 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40819633/ |
| DOI: | https://doi.org/10.1016/j.ebiom.2025.105887 |
| URL: | https://www.thelancet.com/pdfs/journals/ebiom/PIIS2352-3964(25)00331-7.pdf |
Publication 16553
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Abstract
BACKGROUND: Pleural infection is associated with marked local and systemic inflammation leading to significant morbidity. It may be possible to therapeutically augment this response and interleukin-6 is a key signalling cascade in inflammatory pathologies.</p>
METHODS: We performed a prospective observational study recruiting patients with pleural effusions secondary to infection and measured interleukin-6 in matched pleural fluid and serum (n = 76). We subsequently performed a large-scale, two sample Mendelian Randomisation study (1601 cases and 830,709 controls), using genetic variation at IL6R to proxy the effect of interleukin-6 inhibition on pleural infection and overcome confounding inherent in observational analyses.</p>
FINDINGS: Pleural interleukin-6 levels in infection were 5000-fold higher than matched serum levels (median 72,752 pg/ml vs. 15 pg/ml). Pleural interleukin-6 predicted systemic inflammation (neutrophil count, C- reactive protein), correlated with clinical markers of disease severity (effusion size, pH, glucose), and was strongly associated with length of hospital stay. In Mendelian randomisation analyses, interleukin-6 inhibition was predicted to have a large protective effect on the incidence of infection (OR 0.23; 95% CI 0.14-0.39 per standard deviation decrease in C- reactive protein). The effect size was larger than that seen in COVID-19 and coronary artery disease, where interleukin-6 inhibition has been successful in trials.</p>
INTERPRETATION: Multiple lines of evidence suggest pleural interleukin-6 drives pathology in pleural infection. Targeting interleukin-6 may hold promise and should be considered in randomised trials.</p>
FUNDING: This study has been funded by the National Institutes of Health and Care Research Bristol Biomedical Research Centre.</p>
14 Keywords
- Adult
- Aged
- Biomarkers
- Female
- Humans
- Interleukin-6
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Pleural Effusion
- Polymorphism, Single Nucleotide
- Prospective Studies
- Receptors, Interleukin-6
- Signal Transduction
11 Authors
- Amerikos Argyriou
- Alex Robbins
- Rachel Scott
- Jodie Chalmers
- Harrison I.W. Wright
- Robin N. Beaumont
- Karen T. Elvers
- Michael N. Weedon
- Nick A. Maskell
- David T. Arnold
- Fergus W. Hamilton
1 Application
| Application ID | Title |
|---|---|
| 81499 | Using human genetics to develop insight into putative causal relationships between modifiable exposures and disease endpoints |
Enabling scientific discoveries that improve human health