Exposure to ozone contributed to the worsening of inflammation and glucocorticoids insensitivity in OVA-challenged asthma. Interleukin-17A participates centrally in stages of the inflammatory response and glucocorticoids insensitivity. In this study, the effect of neutralizing anti-murine interleukin-17A monoclonal antibody (IL-17A mAb) on inflammation and glucocorticoids insensitivity in ozone-exposed and ovalbumin (OVA)-challenged mice was investigated.

Mice were sensitized and challenged with OVA and then exposed to ozone. Dexamethasone (Dex) and IL-17A mAb were administrated in corresponding periods.

Compared with OVA-challenged mice, combination administration of ozone exposure and OVA challenge increased the recruitment of inflammatory cells in bronchoalveolar lavage fluid, enhanced the inflammation scores and levels of inflammatory cytokines and IL-17A mRNA, and caused the activation of p38 MAPK together with down regulation of glucocorticoids recepters (GR) in lung tissue. Monotherapy of IL-17A mAb partially attenuated lung inflammation in OVA-challenged and ozone-exposed mice, while the combination treatment of Dex and IL-17A mAb effectively reduced lung inflammation, inactivated p38 MAPK and up regulated GR in lung tissue.

Ozone exposure worsened OVA-challenged airway inflammation, activation of p38 MAPK and down regulation of GR in OVA-sensitized and -challenged mice, which was effectively counteracted by IL-17A mAb, and combination treatment of IL-17A mAb and Dex shows profound efficacy in inhibiting airway inflammation and improving glucocorticoids insensitivity synergistically.