Methods: Two kinds of IL-27 intervention were set up, one of which is low-dose-multiple preventive model, the other is high-dose-few times treating model. Airway hyperresponsiveness BAL, HE staining were tested. The mRNA, protein level of STAT1 and GADD45γ were measured through qPCR and western blot.
Results: In low-dose-multiple prevention group, IL-27 inhibits inflammation around bronchial and vascular obviously. In asthma model, OVA-induced airway inflammation impaired both STAT1 phosphorylation and GADD45γ expression which mediate IFN-r producing pathway in the end. IL-27 administration by nasal pre-OVA sensitization could reverse GADD45γ impairment but not STAT1 phosphorylation. At the same time, IL-27 has little effect on alleviating airway inflammation when used post-OVA sensitization.
Conclusions: IL-27 inhibits naïve CD4+ T cells’ Th2 differentiation but not already committed Th2 cell reprogramming. Our model demonstrated IL-27 resistance when used post-OVA sensitization due to existed Th2- induced STAT1 and GADD45γ downregulation. Low-dose-multiple preventive way improve airway inflammation greatly by reversing GADD45γ expression but not STAT1-Py which indicate intervention time-point is critically important in modulating Th1-Th2 balance when using cytokine strategy.