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Eotaxin: a Potential Target for Therapy in Chronic Rhinosinusitis

Eotaxin: a Potential Target for Therapy in Chronic Rhinosinusitis. Alisha N. West, MD Grand Rounds University of California, Los Angeles December 1, 2010. History. Chronic Rhinosinusitis (CRS) is characterized by signs and symptoms of inflammation Stimulated by environmental pathogen

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Eotaxin: a Potential Target for Therapy in Chronic Rhinosinusitis

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  1. Eotaxin: a Potential Target for Therapy in Chronic Rhinosinusitis Alisha N. West, MD Grand Rounds University of California, Los Angeles December 1, 2010

  2. History • Chronic Rhinosinusitis (CRS) is characterized by signs and symptoms of inflammation • Stimulated by environmental pathogen • Chronic epithelial stimulation  immune response with a subset of patients exhibiting eosinophilia • Lack of effective mucociliary clearance • Currently, paucity of effective therapies

  3. History • Chronic Rhinosinusitis is one of the leading causes of annual visits to the Otolaryngologist • 66 million adults in the US reported sinus problems last year • $5.8 billion dollars is spent annually on treatment for CRS • Symptoms usually recur within three months of therapy

  4. Hypothesis Eotaxin plays a role in CRS inflammation and could serve as a potential target for therapy

  5. Background • Eotaxin-1 and 2 implicated in inflammation seen in ABPA and asthma • IL-13 and IL-4 up-regulate production of Eotaxin by epithelial cells • Eotaxin is a chemotactic factor that attracts eosinophils to the site of inflammation • Eosinophils release MBP which has been shown to cause epithelial cell damage in ABPA patients • Toxic levels of MBP have been found in the mucus of CRS patients • Prior to our current project, the role of eosinophils and eotaxin had not been examined in CRS

  6. Materials and Methods • UNC IRB approved protocols • Sinonasal mucosa harvested during endoscopic sinus surgery60 subjects • Tissue embedded in parrifin and H&E stain performed for EOS • Cell culture protocol • Cellular disaggregation • Plated in serum-free media until confluent, dispersion in trypsin • Re-plated on Milicells™ in air-liquid interface media at density of 250,000 cells/Millicell™ • After confluent monolayeraspirate apical media • Washed and re-fed basally for 21 days until ciliated and mucus production • 4 cell cultures/specimen • Apical challenge with Pseudomonas, Staph, and TSB • Basal Media collected, washed and replaced daily 0-96 hours

  7. IL-1beta IL-2 IL-4 IL-5 IL-6 IL-10 IL-12p70 TNF-alpha IFN-gamma G-CSF IP-10 GM-CSF IL-9 IL-13 KC MCP-1 MIP-1a RANTES IL-1a IL-7 IL-15 IL-17 Materials and MethodsLuminex 22-plex battery of Cytokines

  8. Materials and Methods • Alveolar Lavage has demonstrated eosinophilia in ABPA and asthma patients as well as animal models • Endosinus lavage with evaluation of eosinophilia in CRS patients and normal volunteers • Complete cell count and Eosinophil count performed with cytospin

  9. Tissue Harvest

  10. Results

  11. H&E Stain 10xCRS Control

  12. EosinophiliaCRS Control

  13. Eosinophilia in Endosinus Mucosa

  14. Eotaxin ELISA

  15. Luminex Results

  16. Conclusions • There is significant Eosinophilia in CRS endosinus epithelium when compared to normal controls • CRS epithelium produces a higher concentration of eotaxin at baseline and after an infectious challenge when compared to controls • Eotaxin should be investigated as a potential target for therapy in CRS

  17. References

  18. Thank You

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