Methods.Anti-IL-4Rα loaded nanoparticles were administered intrapulmonary to asthmatic mice. Particles distribution within the lungs were then examined and their targeting of specific IL-4R+ inflammatory cells was investigated using MRI and histological analysis (immunohistochemistry, immunofluorescence). Multiple gene expression studies (RT-PCR), flow cytometry, cytokine arrays (Luminex) and histological analyses were performed on treated asthmatic lungs tissue and cells to evaluate the anti-inflammatory responses of these nanocariers.
Results. Targeting and localization of nanocarriers with Perl’s (iron), PEG (anti-PEG antibodies), immunofluorescence (SPIO nanocarriers with FITC labelled antibody) confirmed their localization with anti-IL-4R+ lung inflammatory cells. Following treatment of asthmatic mice with anti-IL-4R nanocarriers, a significant decrease in BAL levels of IL-1β, IL-10, IL-6, IL-13, GM-CSF, IL-5, IL-2, IL-4, MCP-1, IP-10/CXCL-10, MIG and IFN-γ was observed compared to Ova-sensitized mice. BAL levels of lymphocytes, neutrophils and eosinophils decreased significantly (p<0.01) in mice receiving anti-IL-4Ra loaded nanocarriers. Lung inflammation was significantly decreased as observed in histological analysis as well as gene expression of inflammatory cytokines (genes). In addition, a significant decrease in activation and functionality of lung inflammatory cells was observed suing FACS analysis following treatment with the IL-4R-nanocarrier.
Conclusions: Treatment of inflamed lungs with anti-inflammatory IL-4Rα-nanocarriers was safe and efficient in reducing lung inflammation and controlling asthma pathogenesis. This approach could be effective in attaining asthma control in severe cases where alternative approaches for steroids are needed.