IL-17 and Th17-cells as markers of disease progression in pediatric allergic diseases. A therapeutic approach in an “in vitro” model

Rationale: Th17 cells and IL-17 play a role in allergy development and progression. Objective: To investigate whether IL-17-producing Th17 cells characterized systemic and airway inflammation in children with concomitant allergic rhinitis and asthma and whether Budesonide (Bud) and Formoterol (Form), alone or in combination, might provide a therapeutic strategy for controlling the inflammatory events associated with IL-17. Methods: We tested IL-17 levels in plasma (P), nasal wash (NW) and induced sputum (IS) from healthy (HC) and asthmatic children (intermittent=IA or mild-moderate=MA) with concomitant rhinitis (intermittent=IR or persistent=PR). Then we tested the expression of intracellular IL-17, RORt and FOXP3 in peripheral blood T-lymphocytes (PBT-cells) from IA and MA with concomitant IR or PR and the in vitro effect of Bud and Form in combination on IL-17, RORt, and FOXP3 expression in PBT-cells from children with MA and PR. Finally, we tested the levels of IL-8 release from both nasal and bronchial epithelial cells stimulated with NW and IS from children with allergic MA and concomitant PR. Results: We observed significantly increased levels of IL-17 in P, NW and IS from children with MA compared with IA and HC; increased intracellular IL-17 and RORγt and decreased FOXP3 in PBT-cells from subjects with MA compared with IA as well as in children with MA and PR when compared with MA and IR. Bud with Form in vitro treatment significantly reduced IL-17 and RORγt in PBT-cells from children with MA and PR and the effect of IL-17 present in NW and IS from children with MA and PR on IL-8 release in nasal and bronchial epithelial cell lines. Conclusions: IL-17 and Th17-cells are markers of disease phenotype and progression in children with allergic MA and concomitant PR. Budesonide with Formoterol might be useful for a therapeutic approach to control IL-17 mediated allergic disorders.