Friday, 16 October 2015: 14:15 - 14:30
Room R2 ABC (Floor 3) (Coex Convention Center)
Rabih Halwani, PhD
,
Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Asma Sultana, PhD
,
Prince Naif Center for Immunology Research, College of Medicine, King Saud University; Pnhrc, King Saud University, Riyadh, Saudi Arabia
Roaa Al Kufaidi
,
Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Sibtain Afzal
,
Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Rosan Kanana
,
Prince Naif Center for Immunology Research, College of Medicine, King Saud University; Pnhrc, King Saud University, Riyadh, Saudi Arabia
Achraf Al-Faraj, PhD
,
Department of Radiological Sciences, College of Applied Medical Sciences, King Saud University, riyadh, Saudi Arabia
Saleh Al Muhsen, MD
,
Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Background.Optimal asthma symptom control cannot always be achieved in severe cases due to the risk of steroid resistance and lack of response to beta-agonists. Therefore, alternative approaches are needed to achieve reversal of pathological airway remodelling in steroid resistant severe asthma. IL-4 and IL-13 cytokines are critical for asthma pathogenesis as they modulate IgE synthesis, chemokine production, airway eosinophilia, smooth muscle hyperplasia, and mucus production during asthma. During the past decade, several nanoparticles approaches have been developed and tested for efficient drug and anti-inflammatory agents delivery at various body sites during cancer other chronic inflammatory diseases. The current study evaluated the anti-inflammatory responses following intratracheal instillation of functionalized and PEGylated nanocarriers containing blocking anti-IL4Rα antibodies to the inflamed lungs of asthmatic mouse model.
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.
