For IL-17rs8193036 SNP, the homozygote TT genotype and heterozygote CT genotypes were associated with increased ARDS susceptibility and 30-day mortality risk (<i>P</i><0.05).
Moreover, we established a mouse model of lipopolysaccharide- and cecal ligation and puncture-induced ARDS treated with neutralizing antibodies (anti-IL-35 Ebi3 or anti-IL-35 P35); the results showed that lung injury occurred more often than in untreated models and the inflammatory cytokines CXCL-1, tumor necrosis factor alpha, IL-6, and IL-17A increased significantly after neutralizing antibody treatment in bronchoalveolar lavage fluid and serum.
Pulmonary edema, vascular exudation, and neutrophil accumulation were observed in the ARDS model mice, and the levels of inflammatory cytokines including TNF-α, IL-1b, IL-6, and IL-17 were significantly increased.
Finally, we confirmed the clinical relevance and found that IL-17 expression was elevated and associated with the disease severity in patients with ARDS.
These results reveal a previously unexpected role for adaptive immune responses that increase alveolar permeability in ARDS and suggest that αβTh17 cells and IL-17A could be novel therapeutic targets for this currently untreatable disease.