Azithromycin Attenuated Ovalbumin-Dependent Airway Inflammation Is Independent of Ovalbumin-Specific IgE Production
We next quantified the serum concentration of ovalbumin-specific IgE to confirm equal allergen sensitization in all cohorts of mice and to exclude the possibility that azithromycin attenuated the allergic inflammation by altering IgE production.
Naive mice and mice that received only an ovalbumin challenge (without sensitization) produced no ovalbumin-specific IgE. Mice that were sensitized and challenged with ovalbumin had a significant increase in ovalbumin-specific IgE production (699.8 ± 178.2 ng/mL) that was not significantly changed by treatment with PBS solution (885.1 ± 193.8 ng/mL) or azithromycin (829 ± 231.1 ng/mL; p = 0.80).
Azithromycin Attenuated Ovalbumin-Dependent Airway Inflammation Is Associated With Decreased Concentrations of BAL Fluid Inflammatory Mediators
Based on the affect of azithromycin on inflammatory cell influx, we proposed that azithromycin-dependent attenuation of allergic airway inflammation would also be associated with decreased concentration of BAL fluid cytokines and chemokines.
Compared to ovalbumin sensitized and challenged mice treated with PBS solution, treatment with azithromycin attenuated the expression of multiple BAL fluid cytokines, chemokines, and growth factors as measured by multiplex flow cytometry based assay (Fig 3A-F, column 4 vs 5). Importantly, we observed a statistically significant azithromycin- dependent decrease in interleukin (IL)-13 and IL-5, and a trend toward a decrease in IL-4, proteins known to mediate allergic airway inflammatory phenotypes in the airway (eg, mucous cell metaplasia and eosinophilic inflammation).
In addition, azithromycin attenuated the expression of multiple other chemokines and inflammatory mediators (CCL2/JE, CCL3/macrophage inhibitory protein [MIP]-1a, CCL4/MIP-1P, CXCL1/KC, IL-1a, IL-10, and granulocyte-macrophage colony-stimulating factor), but had no effect on concentration of IL-6, IL-9.
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