Evaluation of cytokines in nasal secretions after nasal antigen challenge: lack of influence of antihistamines

Background: Previous studies of inflammation in allergic rhinitis using nasal irrigation have been unsatisfactory because of 1) poor reproducibility; 2) the tendency of irrigation to overdilute mediators; and 3) the failure of this technique to evaluate interstitial concentrations of relevant mediators. For this study we used filter paper as a matrix to collect nasal secretions in patients undergoing nasal antigen challenge. Objective: To evaluate inflammatory mediators of allergen-induced rhinitis during a clinical trial of fexofenadine. Methods: Subjects evaluated at a referral medical center were placed on traditional dosing of fexofenadine at 60 mg, twice daily, or placebo in a double-blind, crossover fashion for 1 week before the nasal challenge. Nasal challenge was performed with nasal insufflation of either 1,000 AU timothy or 0.1 mL ragweed (1:100 wt/vol) extract outside the pollen season. Nasal secretions were collected at baseline and then at 2, 4, and 6 hours after nasal challenge. Secretions were evaluated for expression of the cellular adhesion molecule-1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-10, macrophage inflammatory protein (MIP)-1alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) using commercially available enzyme-linked immunoadsorbent assay kits. Patients' symptom scores were evaluated during the nasal challenge. Results: Significantly (P < 0.05) increased peak levels of TNF-α, IL-4, IL-40, and MIP-1α were detected after antigen challenge as compared with baseline levels. There was a nonsignificant trend toward an increase in GM-CSF after antigen challenge (P = 0.07). There was no difference in the peak levels of TNF-α, IL-4, IL-10, MIP-1α, or GM-CSF measured when patients were on fexofenadine versus placebo. Finally, there were no significant differences in patients' symptom scores during antigen challenge when subjects were on fexofenadine versus placebo. Conclusions: Collection of nasal secretions using a filter paper matrix provides a reproducible model for accurately detecting and evaluating changes in cytokine levels after nasal challenge. Cytokine levels tend to peak 3 to 4 hours after antigen challenge. Standard doses of fexofenadine do not seem to have a mitigating effect on the production of these cytokines. Symptoms of allergic rhinitis using this type of antigen challenge did not differ from treatment with fexofenadine versus placebo.