Interleukin-17 And Lung Host Defense Against P.aeruginosa Pneumonia Infection

Objective:Interleukin (IL)-17 is a novel cytokine secreted by activated Thl7 cells. It can stimulate CXC chemokine and contributes to host defense through its promoting effects on neutrophil recruitment and activation and the subsequent enhanced clearance of the pathogens. The present study aimed to determine whether IL-17 plays an important role in host defense against Pseudomonas aeruginosa and whether genetic up-regulation of IL-17 could ameliorate acute Pseudomonas aeruginosa lung infection in mice.Methods:We use a murine model of acute P. aeruginosa lung infection that has been previously used, histopathological changes of the lungs, inflammatory cells in BALF, and the levels of cytokines (IL-17, IL-1β, MIP-2, G-CSF)were measured. Plasmid-encoding mIL-17 was delivered to lungs in vivo at 48 h before challenging with P. aeruginosa, bacterial loads, levels of cytokines/chemokines (IL-1β, MIP-2, G-CSF) and the survivals were measured at 6 hours post-infection.Results:IL-17 is highly produced in the lung after challenging with P. aeruginosa. Administration of a plasmid encoding mIL-17 to the lungs of normal mice can stimulate the local release of IL-1β, MIP-2 and G-CSF, which resulted in recruitment of neutrophils into the lung. On the basis of these data, overexpression of IL-17 in the pulmonary compartment using the plasmid resulted in the local induction of tumor IL-1β, MIP-2, G-CSF, augmented recruitment and enhanced bacterial clearance and survival after challenging with P. aeruginosa.Conclusions:Our findings indicate IL-17 may have a role in priming for enhanced chemokine (IL-1β, MIP-2 and G-CSF)and neutrophils production in the context of lung infection and that optimally timed gene therapy with IL-17 may augment host defense against bacterial pneumonia.