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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Autores principales: Toshiyuki Aokage, Mizuki Seya, Takahiro Hirayama, Tsuyoshi Nojima, Masumi Iketani, Michiko Ishikawa, Yasuhiro Terasaki, Akihiko Taniguchi, Nobuaki Miyahara, Atsunori Nakao, Ikuroh Ohsawa, Hiromichi Naito
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spelling 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 DOAJ
collection 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.
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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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