REMOTE ischemic conditioning significantly reduced pulmonary fibrosis pathology in a diesel exhaust-induced mouse model, improving physiological measures, lowering inflammatory and fibrotic markers, and restoring mitochondrial health.
These findings suggest that this non-pharmacological intervention could have therapeutic potential in pulmonary fibrosis.
Researchers evaluated remote ischemic conditioning in mice with pulmonary fibrosis induced by prolonged diesel exhaust exposure.
The intervention was delivered either before or during disease development and was compared with both untreated disease and treatment with pirfenidone.
Across multiple physiological and molecular assessments, mice receiving remote ischemic conditioning demonstrated clear improvements compared with untreated animals.
Body weight and heart rate variability, both adversely affected by diesel exhaust exposure, improved in groups receiving the intervention.
Histopathological analysis also revealed reduced cellular infiltration, less bronchiolar inflammation, and fewer structural abnormalities within lung tissue.
These changes indicated attenuation of key pulmonary fibrosis features.
The therapeutic benefits of remote ischemic conditioning were also reflected in circulating biomarkers associated with pulmonary fibrosis.
Mice receiving the intervention showed significantly lower levels of actin alpha 2 smooth muscle, brain natriuretic peptide, surfactant protein-D, Krebs von den Lungen-6, and collagen type 1 alpha 1 compared with untreated animals.
Evaluation of bronchoalveolar lavage fluid demonstrated reduced inflammatory activity.
Total leukocyte counts were lower in treated groups, while concentrations of interleukin-1β, interleukin-13, and interleukin-17A were significantly decreased.
Together, these findings suggest that the intervention alleviated inflammatory processes linked to fibrosis progression.
Researchers also observed improvements in mitochondrial function.
Treated mice exhibited higher mitochondrial membrane potential and lower cellular reactive oxygen species levels, indicating healthier mitochondrial activity and reduced oxidative stress.
Transcriptomic analysis provided further evidence supporting the intervention.
Lung tissue from mice receiving remote ischemic conditioning showed downregulation of multiple pulmonary fibrosis-associated pathways related to immune regulation, extracellular matrix organisation, connective tissue development, and cellular bioenergetics.
Several pulmonary fibrosis-related genes were suppressed in treated groups, while genes associated with tissue recovery and pulmonary health were upregulated.
The researchers also identified several potential fibrosis-associated markers, including Calhm6, Hrc, Dnase1l3, Pla2g2d, Stab2, and Timd4, which may contribute to future investigations into disease mechanisms and treatment response.
Notably, the combination of remote ischemic conditioning with pirfenidone produced the lowest overall fibrotic burden across treatment groups.
The researchers concluded that remote ischemic conditioning may represent a promising adjunctive strategy for pulmonary fibrosis and warrants further translational research.
Reference
Kumari S et al. Remote ischemic conditioning mitigates diesel exhaust-induced pulmonary fibrosis by alleviating pulmonary inflammation and fibrogenesis. Sci Rep. 2026;DOI:10.1038/s41598-026-72674-w.
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