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Protective effect of recombinant interleukin-10 on newborn rat lungs exposed to short-term sublethal hyperoxia

Clin Exp Pediatr > Epub ahead of print
DOI: https://doi.org/10.3345/cep.2024.01221    [Epub ahead of print]
Published online September 27, 2024.
Protective effect of recombinant interleukin-10 on newborn rat lungs exposed to short-term sublethal hyperoxia
Hyeon-Soo Lee1  , Young-Joon Ryu2  , Min-Jae Lee3 
1Department of Pediatrics, Uijeongbu Eulji Medical Center, Eulji University College of Medicine, Uijeongbu, Korea
2Clinical Pathology, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
3College of Veterinary Medicine, Kangwon National University, Chuncheon, Korea
Correspondence: 
Hyeon-Soo Lee, Email: premee@eulji.ac.kr
Received: 20 August 2024   • Revised: 19 September 2024   • Accepted: 19 September 2024
Abstract
Background
Lung injury imposed by hyperoxia is the main cause of bronchopulmonary dysplasia in newborns. These injuries are generated from the early stage of hyperoxia through the main biologic effects of cell death and inflammatory response. Interleukin (IL)-10 is a potent anti-inflammatory cytokine that may have the inhibitory effects on these biologic actions induced by hyperoxia.
Purpose
Based on our former in vitro studies investigating the effect of recombinant IL-10 (rIL-10) on protecting cultured alveolar type II cells exposed to short-term hyperoxia, we performed the in vivo study to investigate the effect of rIL-10 in newborn rats aged P4 exposed to hyperoxia.
Methods
Rats were classified into 3 groups; the control group exposed to normoxia for 24 hours; the hyperoxia group exposed to 65% hyperoxia for 24 hours; and the IL10 group treated with intratracheal instillation of rIL-10 prior to exposure to 65% hyperoxia for 24 hours. Following each treatment, the rats were euthanized. Individual lobes of the right lung were prepared for hematoxyling and eosin (H&E) staining and immunohistochemical staining for thyroid transcription factor-1 (TTF1). Bronchoalveolar lavage (BAL) was performed in the left lung to analyze cell counts and cytokines.
Results
The IL10 group showed preserved air spaces similar to the control group, with decreased cellularity compared to the hyperoxia group, whereas the hyperoxia group showed markedly reduced air spaces with increased cellularity compared to the IL10 group. And, the IL10 group showed more TTF1-positive cells, which represented alveolar type II cells, compared to the hyperoxia group. Inflammatory cells, such as neutrophils and lymphocytes and proinflammatory cytokines of tumor necrosis factor-α, IL-1α, IL-8, and macrophage inflammatory protein-1α were significantly lower in BAL fluid of the IL10 group compared to the hyperoxia group.
Conclusion
These results indicate that rIL-10 may be a promising pharmaceutical measure for protecting newborn lungs from injury induced at the early stage of hyper oxia.
Key Words: Recombinant IL-10, Hyperoxia, Newborn rat lungs


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