title: Exogenous interleukin-10 attenuates hyperoxia-induced acute lung injury in mice.
abstract: What is the central question of this study? It is not known whether treatment with interleukin-10 (IL-10) attenuates hyperoxia-induced acute lung injury in mice. What is the main finding and its importance? Our results showed that exogenous IL-10 treatment alleviated hyperoxia-induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases. Lung injury caused by breathing air enriched with oxygen continues to be a major problem in clinical medicine. Here, we investigated the therapeutic role of interleukin-10 (IL-10) in hyperoxia-induced acute lung injury in mice. In the first experiment, mice were exposed to room air or 95% O2 and treated with IL-10 simultaneously. In the second experiment, wild-type mice and IL-10(-/-) mice were exposed to room air or 95% O2 . Exogenous IL-10 treatment attenuated hyperoxia-induced acute lung injury, evidenced by a reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, cell numbers and protein content in bronchoalveolar lavage fluid and cell death. Interleukin-10 treatment markedly prolonged the survival of mice during oxygen exposure. Interleukin-10 treatment reduced the activity of myeloperoxidase and mRNA levels of interleukin-6, tumour necrosis factor-α and macrophage inflammatory protein 2, suppressed nuclear factor-κB activation and decreased inducible nitric oxide synthnase expression and nitric oxide formation in lungs of mice exposed to hyperoxia. Interleukin-10 treatment suppressed activities of matrix metalloproteinase 2 and matrix metalloproteinase 9 and reduced lung permeability in mice during oxygen exposure. Furthermore, absence of IL-10 aggravated hyperoxia-induced acute lung injury and reduced the duration of survival of mice during oxygen exposure, which was attenuated by treatment with IL-10. In conclusion, our results show that exogenous IL-10 treatment alleviates hyperoxia-induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases. This suggests that IL-10 treatment may be a promising therapeutic strategy to reduce lung injury in patients exposed to hyperoxia.
authors.affiliation: Department of Respiratory Disease, the 88th Hospital of the Chinese PLA, Taian, 271000, China.
authors.forename: Huai-Dong
authors.initials: HD
authors.lastname: Li
authors.forename: Qing-Xiang
authors.initials: QX
authors.lastname: Zhang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Mao
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Xu
authors.forename: Nai-Yi
authors.initials: NY
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D016923:Cell Death / Q000187:drug effects; D054426:Chemokine CXCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; C556062:IL10 protein, mouse; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010100:Oxygen