TY - JOUR
T1 - The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury
AU - Aokage, Toshiyuki
AU - Seya, Mizuki
AU - Hirayama, Takahiro
AU - Nojima, Tsuyoshi
AU - Iketani, Masumi
AU - Ishikawa, Michiko
AU - Terasaki, Yasuhiro
AU - Taniguchi, Akihiko
AU - Miyahara, Nobuaki
AU - Nakao, Atsunori
AU - Ohsawa, Ikuroh
AU - Naito, Hiromichi
N1 - Funding Information:
This study was supported by a grant from the JSPS KAKENHI, Grant Number 19K09416, and Teijin Pharma Limited, Grant Number TJNS20190415006.
Funding Information:
We thank Toshiyuki Ishiwata (Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan) for provision and technical guidance using the Mantra System and InForm software. We thank Shannon Wyszomierski, PhD for editing the manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Acute respiratory distress syndrome
KW - Bleomycin-induced lung injury
KW - Lung fibrosis
KW - Macrophage
KW - Molecular hydrogen
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U2 - 10.1186/s12890-021-01712-2
DO - 10.1186/s12890-021-01712-2
M3 - Article
C2 - 34719405
AN - SCOPUS:85118300229
VL - 21
JO - BMC Pulmonary Medicine
JF - BMC Pulmonary Medicine
SN - 1471-2466
IS - 1
M1 - 339
ER -