IL-17A-induced neutrophilic airway inflammation is mediated by oxidant-antioxidant imbalance and inflammatory cytokines in mice.

IL-17 A is produced by several innate and adaptive immune cells which include Th17, and innate lymphoid 3 cells in the lung. IL-17 A can activate airway epithelial cells (AECs), through IL-17 receptor (IL-17R) leading to production of chemokines/cytokines. Inflammatory nature of IL-17 A and its signaling has been assessed by several studies using IL-17 A/IL-17R knockout mice which show attenuated inflammation in different disease models. IL-17 A/IL-17R signaling also plays an important role in pulmonary inflammation through recruitment of neutrophils. However, effect of IL-17 A on oxidant-antioxidant balance in the lung and its association with pulmonary inflammation has not been evaluated earlier. Our study evaluated the effect of intranasal administration of IL-17 A on oxidant-antioxidant balance [inducible nitric oxide synthase (iNOS), nitrotyrosine, lipid peroxides, glutathione peroxidase, and total glutathione levels] and chemokines/cytokines expression (IL-6, MCP-1, and MIP-2) in the lung/AECs and their modulation by an antioxidant, N-acetyl cysteine (NAC). Our study shows that IL-17 A administration leads to increased neutrophilic inflammation along with concomitant increase in iNOS and nitrotyrosine/lipid peroxides. On the other hand, there was a reduction in GPx activity and total thiol levels after IL-17 A administration. IL-17 A administration also led to increased IL-6/MCP-1/MIP-2. IL-17A-induced oxidative stress/IL-6 expression and neutrophilic inflammation was attenuated by NAC treatment, whereas there was no effect on chemokines. This suggests that antioxidant NAC attenuates IL-17A-induced pulmonary inflammation by restoring oxidant-antioxidant balance and attenuation of IL-6 in the lung. Further, our study suggests that inflammatory pulmonary disorders which involve increase in IL-17 A may be ameliorated by NAC treatment.