Oxidants are generated in asthmatic airways due to infiltration of inflammatory leukocytes and resident cells in the lung.
Reactive oxygen species (ROS) such as
hydrogen peroxide and
superoxide radical may leak into systemic circulation when generated in uncontrolled manner and may impact vasculature. Our previous studies have shown an association between airway
inflammation and systemic
inflammation; however so far none has investigated the impact of airway oxidative
inflammation on hepatic oxidative stress and Th1/Th2/Th17
cytokine markers in liver/vasculature in a murine model of
asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of systemic/hepatic Th1/Th2/Th17
cytokines balance and hepatic oxidative stress. Mice were sensitized intraperitoneally with cockroach extract (CE) in the presence of
aluminum hydroxide followed by several intranasal (i.n.) challenges with CE. Mice were then assessed for systemic/hepatic
inflammation through assessment of Th1/Th2/Th17
cytokines and oxidative stress (iNOS,
protein nitrotyrosine,
lipid peroxides and
myeloperoxidase activity). Challenge with CE led to increased Th2/Th17
cytokines in blood/liver and hepatic oxidative stress. However, only Th17 related pro-inflammatory markers were upregulated by
hydrogen peroxide (H2O2) inhalation in vasculature and liver, whereas
antioxidant treatment, N-acetyl
cysteine (NAC) downregulated them. Hepatic oxidative stress was also upregulated by H2O2 inhalation, whereas NAC attenuated it. Therefore, our study shows that airway oxidative
inflammation may contribute to systemic
inflammation through upregulation of Th17 immune responses in blood/liver and hepatic oxidative stress. This might predispose these patients to increased risk for the development of cardiovascular disorders.