Anti-PD-1 exacerbates bleomycin-induced lung injury in mice via Caspase-3/GSDME-mediated pyroptosis
2025

Anti-PD-1 and Bleomycin Cause Lung Injury in Mice

Sample size: 45 publication 10 minutes Evidence: moderate

Author Information

Author(s): Wang Fei, Deng Haiyi, Zhou Maolin, Yang Yilin, Zhou Jiankui, Wang Yansheng, Xie Xiaohong, Lin Xinqing

Primary Institution: First Affiliated Hospital of Guangzhou Medical University

Hypothesis

Does GSDME-mediated pyroptosis contribute to lung injury caused by anti-PD-1 treatment in mice?

Conclusion

The study found that GSDME-mediated pyroptosis is linked to increased lung injury when anti-PD-1 is combined with bleomycin in mice.

Supporting Evidence

  • Anti-PD-1 treatment combined with bleomycin led to more severe lung inflammation and fibrosis in mice.
  • High levels of caspase-3 and GSDME were found in the lung tissue of treated mice.
  • SP600125, a JNK inhibitor, reduced lung damage by inhibiting pyroptosis.
  • RNA sequencing showed upregulation of pyroptosis-related genes in lung tissue from ICI-LI patients.

Takeaway

When mice were given a drug that helps fight cancer, it made their lungs hurt more when they also got another medicine that causes lung damage.

Methodology

Mice were treated with bleomycin and anti-PD-1 antibodies, followed by assessments of lung function, histology, and gene expression.

Limitations

The complexity of ICI-LI mechanisms cannot be fully replicated in vitro.

Statistical Information

P-Value

0.04

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1038/s41419-024-07319-9

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