The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury
Abstract Background Acute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory propert...
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oai:doaj.org-article:58f7a2d72e1948ee941a0ae606f858662021-11-08T11:13:19ZThe effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury10.1186/s12890-021-01712-21471-2466https://doaj.org/article/58f7a2d72e1948ee941a0ae606f858662021-10-01T00:00:00Zhttps://doi.org/10.1186/s12890-021-01712-2https://doaj.org/toc/1471-2466Abstract Background Acute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory properties, we hypothesized that daily repeated inhalation of hydrogen gas could suppress persistent lung inflammation by inducing functional changes in macrophages, and consequently inhibit lung fibrosis during late-phase lung injury. Methods To test this hypothesis, lung injury was induced in mice by intratracheal administration of bleomycin (1.0 mg/kg). Mice were exposed to control gas (air) or hydrogen (3.2% in air) for 6 h every day for 7 or 21 days. Respiratory physiology, tissue pathology, markers of inflammation, and macrophage phenotypes were examined. Results Mice with bleomycin-induced lung injury that received daily hydrogen therapy for 21 days (BH group) exhibited higher static compliance (0.056 mL/cmH2O, 95% CI 0.047–0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH2O, 95% CI 0.031–0.053, p = 0.02) and lower static elastance (BH 18.8 cmH2O/mL, [95% CI 15.4–22.2] vs. BA 26.7 cmH2O/mL [95% CI 19.6–33.8], p = 0.02). When the mRNA levels of pro-inflammatory cytokines were examined 7 days after bleomycin administration, interleukin (IL)-6, IL-4 and IL-13 were significantly lower in the BH group than in the BA group. There were significantly fewer M2-biased macrophages in the alveolar interstitium of the BH group than in the BA group (3.1% [95% CI 1.6–4.5%] vs. 1.1% [95% CI 0.3–1.8%], p = 0.008). Conclusions The results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury.Toshiyuki AokageMizuki SeyaTakahiro HirayamaTsuyoshi NojimaMasumi IketaniMichiko IshikawaYasuhiro TerasakiAkihiko TaniguchiNobuaki MiyaharaAtsunori NakaoIkuroh OhsawaHiromichi NaitoBMCarticleAcute respiratory distress syndromeBleomycin-induced lung injuryMacrophageMolecular hydrogenLung fibrosisDiseases of the respiratory systemRC705-779ENBMC Pulmonary Medicine, Vol 21, Iss 1, Pp 1-15 (2021) |
institution |
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DOAJ |
language |
EN |
topic |
Acute respiratory distress syndrome Bleomycin-induced lung injury Macrophage Molecular hydrogen Lung fibrosis Diseases of the respiratory system RC705-779 |
spellingShingle |
Acute respiratory distress syndrome Bleomycin-induced lung injury Macrophage Molecular hydrogen Lung fibrosis Diseases of the respiratory system RC705-779 Toshiyuki Aokage Mizuki Seya Takahiro Hirayama Tsuyoshi Nojima Masumi Iketani Michiko Ishikawa Yasuhiro Terasaki Akihiko Taniguchi Nobuaki Miyahara Atsunori Nakao Ikuroh Ohsawa Hiromichi Naito The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury |
description |
Abstract Background Acute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory properties, we hypothesized that daily repeated inhalation of hydrogen gas could suppress persistent lung inflammation by inducing functional changes in macrophages, and consequently inhibit lung fibrosis during late-phase lung injury. Methods To test this hypothesis, lung injury was induced in mice by intratracheal administration of bleomycin (1.0 mg/kg). Mice were exposed to control gas (air) or hydrogen (3.2% in air) for 6 h every day for 7 or 21 days. Respiratory physiology, tissue pathology, markers of inflammation, and macrophage phenotypes were examined. Results Mice with bleomycin-induced lung injury that received daily hydrogen therapy for 21 days (BH group) exhibited higher static compliance (0.056 mL/cmH2O, 95% CI 0.047–0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH2O, 95% CI 0.031–0.053, p = 0.02) and lower static elastance (BH 18.8 cmH2O/mL, [95% CI 15.4–22.2] vs. BA 26.7 cmH2O/mL [95% CI 19.6–33.8], p = 0.02). When the mRNA levels of pro-inflammatory cytokines were examined 7 days after bleomycin administration, interleukin (IL)-6, IL-4 and IL-13 were significantly lower in the BH group than in the BA group. There were significantly fewer M2-biased macrophages in the alveolar interstitium of the BH group than in the BA group (3.1% [95% CI 1.6–4.5%] vs. 1.1% [95% CI 0.3–1.8%], p = 0.008). Conclusions The results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury. |
format |
article |
author |
Toshiyuki Aokage Mizuki Seya Takahiro Hirayama Tsuyoshi Nojima Masumi Iketani Michiko Ishikawa Yasuhiro Terasaki Akihiko Taniguchi Nobuaki Miyahara Atsunori Nakao Ikuroh Ohsawa Hiromichi Naito |
author_facet |
Toshiyuki Aokage Mizuki Seya Takahiro Hirayama Tsuyoshi Nojima Masumi Iketani Michiko Ishikawa Yasuhiro Terasaki Akihiko Taniguchi Nobuaki Miyahara Atsunori Nakao Ikuroh Ohsawa Hiromichi Naito |
author_sort |
Toshiyuki Aokage |
title |
The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury |
title_short |
The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury |
title_full |
The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury |
title_fullStr |
The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury |
title_full_unstemmed |
The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury |
title_sort |
effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury |
publisher |
BMC |
publishDate |
2021 |
url |
https://doaj.org/article/58f7a2d72e1948ee941a0ae606f85866 |
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