Reduced eosinophil pro-fibrogenic effect in severe childhood asthma compared to mild disease: An effect of corticosteroids?

Eosinophils play an important role in inflammation and probably in airway remodeling in asthma. We previously demonstrated that eosinophils from atopic subjects display profibrogenic properties towards lung fibroblasts partially by preformed transforming growth factor-β (TGF-β). We hypothesized that the pro-fibrogenic potential of eosinophils is increased in children with life-threatening asthma (LTA). Six children with atopic LTA clinically well-controlled by inhaled corticosteroids (ICS) and 5 children with atopic mild asthma (MA) treated only with inhaled β₂-agonists were investigated. The effects of their peripheral blood eosinophils on fibroblast proliferation and lattice contraction were investigated. In addition, TGF-β₁ and IL-6 eosinophil content were also evaluated. Unexpectedly, eosinophils from LTA increased fibroblast proliferation (5.4-fold) and gel contraction (1.1-fold) significantly less than those from MA. TGF-β₁ but not IL-6 eosinophil content in LTA was significantly lower than that in MA (2.7-fold). In vitro, addition of dexamethasone on eosinophils stimulated by mast cells resulted in a marked decrease in their TGF-β₁ content by 1.6-fold. In conclusion, eosinophils from children with ICS-treated LTA displayed significantly less pro-fibrogenic properties than those from MA treated only with β₂-agonists. Our data suggest that the pro-fibrogenic effect of eosinophils might be influenced by treatment with ICS in childhood asthma.