Role of reactive persulfide species in influenza virus-induced lung inflammation

Rationale: Influenza virus is one of the most common respiratory pathogens. Oxidative stress is reportedly involved in the virus-induced lung inflammation. Reactive persulfide species (RSS) such as cysteine persulfide have recently been recognized as potent endogenous antioxidants and shown to exist in lung. Methods: Wild type (WT) or RSS synthetase deficiency mice were given an intratracheal instillation of influenza virus A (H1N1). Bronchoalveolar lavage fluid (BALF) was obtained for the evaluation of airway inflammation. Lungs of the mice after exposure to influenza virus were obtained for pathological evaluation. Inflammatory cytokines including interleukin (IL) -6 and tumor necrosis factor (TNF)-α in BALF were measured using cytometric bead arrays. Furthermore, the effect of exogenous RSS donor on the survival and inflammatory status of the mice was investigated. Results: The survival rate of RSS synthetase deficiency mice treated with influenza virus A was significantly lower than that of WT mice. The numbers of inflammatory cells such as neutrophils and lymphocytes, and the concentrations of inflammatory cytokines were significantly increased in the BALF or the lungs from the synthetase deficiency mice compared to those from WT mice. An RSS donor significantly restored the survival rate of WT mice exposed to influenza virus A, and also reduced the number of inflammatory cells and the amounts of cytokines in BALF from the mice. Conclusion: These data suggest that a decrease of RSS in lung might contribute to the pathogenesis of lung inflammation induced by influenza virus, which could be a promising therapeutic target.