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 irrication 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-alpha, IL-4, IL-10, and MIP-1alpha 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-alpha, IL-4, IL-10, MIP-1alpha, 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.
Bensch
Greg W
GW
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA.
Nelson
Harold S
HS
Borish
Larry C
LC
D000293:Adolescent; D000328:Adult; D000368:Aged; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018592:Cross-Over Studies; D016207:Cytokines / Q000032:analysis*; D004311:Double-Blind Method; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism*; D009299:Nasal Provocation Tests; D010940:Plant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012221:Rhinitis, Allergic, Perennial / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018926:Anti-Allergic Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D006634:Histamine H1 Antagonists; D019402:Macrophage Inflammatory Proteins; D010940:Plant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D016593:Terfenadine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C093230:fexofenadine