The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury

BMC Pulmonary Medicine

Yasuhiro Terasaki¹  Masumi Iketani²  Ikuroh Ohsawa²  Takahiro Hirayama³  Hiromichi Naito⁴  Atsunori Nakao⁴  Toshiyuki Aokage⁴  Mizuki Seya⁴  Michiko Ishikawa⁵  Akihiko Taniguchi⁶  Nobuaki Miyahara⁷  Tsuyoshi Nojima⁸ 

[1] Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan;Department of Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan;Department of Disaster Medicine and Management, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, 700-8558, Okayama-shi, Okayama, Japan;Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Japan;Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;Department of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama, Japan;Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;

关键词: Acute respiratory distress syndrome;    Bleomycin-induced lung injury;    Macrophage;    Molecular hydrogen;    Lung fibrosis;   

DOI  :  10.1186/s12890-021-01712-2

来源: Springer

【 摘 要 】

BackgroundAcute 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.MethodsTo 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.ResultsMice 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).ConclusionsThe results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury.

【 授权许可】

CC BY