Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma.
Interleukin (IL)-17 is produced by activated memory CD4(+) cells and induces cytokines and chemokines that stimulate neutrophil generation and recruitment. Here, we investigated the involvement of IL-17 in the bronchial influx of neutrophils in experimental allergic asthma. Inhalation of nebulized ovalbumin (OVA) by sensitized mice with bronchial eosinophilic inflammation resulting from chronic OVA exposure induced early IL-17 mRNA expression in inflamed lung tissue, concomitant with a prominent bronchial neutrophilic influx. Anti-IL-17 monoclonal antibodies (mAb) injected before allergen inhalation strongly reduced bronchial neutrophilic influx, in a manner equally as potent as the anti-inflammatory dexamethasone. Remarkably, anti-IL-17 mAb significantly enhanced IL-5 levels in both BAL fluid and serum, and aggravated allergen-induced bronchial eosinophilia. In another series of experiments, anti-IL-17 mAb were given repeatedly during the inhalatory challenge phase with OVA of sensitized mice. This treatment regimen abated bronchial neutrophilia in parallel with reduction of bone marrow and blood neutrophilia. In addition, anti-IL-17 mAb treatment elevated eosinophil counts in the bone marrow and bronchial IL-5 production, without alteration of allergen-induced bronchial hyperresponsiveness. In summary, our results demonstrate that IL-17 expression in airways is upregulated upon allergen inhalation, and constitutes the link between allergen-induced T cell activation and neutrophilic influx. Because neutrophils may be important in airway remodeling in chronic severe asthma, targeting IL-17 may hold therapeutic potential in human asthma.
Hellings
Peter W
PW
Laboratory of Experimental Immunology, Rega Institute, University of Leuven, Leuven, Belgium.
Kasran
Ahmad
A
Liu
Zhanju
Z
Vandekerckhove
Philippe
P
Wuyts
Anja
A
Overbergh
Lutgart
L
Mathieu
Chantal
C
Ceuppens
Jan L
JL
D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D001980:Bronchi / Q000276:immunology / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D002465:Cell Movement / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D004802:Eosinophilia / Q000276:immunology / Q000503:physiopathology; D006098:Granulocytes / Q000166:cytology*; D020381:Interleukin-17 / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal
D000485:Allergens; D000911:Antibodies, Monoclonal; D016207:Cytokines; D017931:DNA Primers; D020381:Interleukin-17