Lethal concentration of perfluoroisobutylene induces acute lung injury in mice mediated via cytokine storm, oxidative stress and apoptosis

Abstract

Perfluoroisobutylene (PFIB) is a highly toxic gas that targets the lungs. Low-level inhalation of the gas can lead to acute lung injury (ALI), pulmonary edema and even death. No specific anti-PFIB drugs are currently available and the pathogenesis of PFIB-induced ALI is not fully understood. Early direct oxidative injury and a secondary hyper-inflammatory response are recognized as the primary mechanisms of PFIB-induced ALI. In the present study, our data demonstrate for the first time that a cytokine storm is associated with PFIB-induced ALI. Levels of 10 pro-inflammatory cytokines and one anti-inflammatory cytokine were significantly increased in lung tissues of PFIB-exposed mice. PFIB inhalation additionally led to significant oxidative stress in lung tissue. Inflammation-associated CD11b⁺Ly6G⁺Ly6C^int neutrophils and CD11b⁺Ly6G^-Ly6C^hi monocytes were significantly increased in blood in association with PFIB-induced ALI. Bcl-2/Bax-mediated lung cell apoptosis was significantly increased at 1 h, followed by a sustained decrease after 1 h, which was significant at 4–8 h in PFIB-exposed mice. This suppression of apoptosis is possibly associated with the Akt-signaling pathway.

Keywords:

• Perfluoroisobutylene
• acute lung injury
• cytokine storm
• oxidative stress
• apoptosis

Acknowledgements

We wish to thank the Department of Pathology, 210th Hospital of the Chinese People’s Liberation Army for histopathologic analysis.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by the China Postdoctoral Science Foundation [No. 2015M572801]. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.