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 pro-fibrogenic properties towards lung fibroblasts partially by preformed transforming growth factor-beta (TGF-beta). 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 beta(2)-agonists were investigated. The effects of their peripheral blood eosinophils on fibroblast proliferation and lattice contraction were investigated. In addition, TGF-beta(1) 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-beta(1) 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-beta(1) 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 beta(2)-agonists. Our data suggest that the pro-fibrogenic effect of eosinophils might be influenced by treatment with ICS in childhood asthma.
Puxeddu
Ilaria
I
Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Lack
Gideon
G
Smith
Susan J
SJ
Levi-Schaffer
Francesca
F
D000085:Acetates / Q000627:therapeutic use; D000293:Adolescent; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D002648:Child; D003521:Cyclopropanes; D003907:Dexamethasone / Q000627:therapeutic use; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D000068298:Fluticasone; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011804:Quinolines / Q000627:therapeutic use; D000068299:Salmeterol Xinafoate; D013440:Sulfides
D000085:Acetates; D000730:Androstadienes; D003521:Cyclopropanes; D005938:Glucocorticoids; D011804:Quinolines; D013440:Sulfides; D000068299:Salmeterol Xinafoate; D003907:Dexamethasone; D000068298:Fluticasone; C093875:montelukast; D000420:Albuterol