Background

Eosinophils play critical roles in the development of allergic rhinitis (AR) by releasing toxic substance. Interleukin-35 (IL-35), a newly identified anti-inflammatory cytokine, had potent inhibitive role for eosinophil infiltration in allergic disease. However, the direct effect of IL-35 on eosinophil was not clear.

Methods

Twenty AR children and sixteen controls were recruited. The correlation between IL-35 protein expression and blood eosinophils counts and activation was analyzed. The effect of IL-35 on eosinophil apoptosis and adhesion were analyzed by flow cytometry. Transwell system was used for the migration assay. The eosinophil cationic protein (ECP) from supernatant of eosinophils after IL-35 stimulation were detected by enzyme linked immunosorbent assay kits.

Results

The IL-35 protein levels were negatively correlated with eosinophils counts (P<0.01) and ECP concentration (P<0.01) in AR children. IL-35 promotes apoptosis, inhibits adhesion, migration and activation of eosinophils. Moreover, the mRNA expression of IL-12 receptor β2 and glycoprotein 130 were significantly enhanced by eosinophils after IL-35 stimulation. The apoptosis induced by IL-35 was mediated by phosphoinositide 3-kinase (PI3K) pathway. IL-35 inhibits adhesion of eosinophils through extracellular regulated protein kinases (ERK) and PI3K pathways. The eosinophil chemotaxis and activation affected by IL-35 were mediated by PI3K and p38 mitogen-activated protein kinase (MAPK) pathways.

Conclusion

Our results confirmed that IL-35 played inhibitive roles in apoptosis, adhesion, migration and activation of eosinophils in AR, implying that IL-35 may be used as treatment target in future.