1 LPS administration to the allergic nose contributes to lower airway inflammation

_____________________________________________ _____ This is an author produced version of a paper published in Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. "Lipopolysaccharide administration to the allergic nose contributes to lower airway inflammation" Access to the published version may require journal subscription. Running head: A priming effect of allergen on nasal responsiveness to LPS Summery Background Allergic rhinitis is an inflammatory reaction not confined to a single local compartment, but rather involving the whole airway system. Allergens known to induce allergic rhinitis are not always the sole trigger of the inflammatory reaction. Infections and organic dust might also cause exacerbations of rhinitis and associated conditions. Objective To examine the effects of intranasal LPS exposure, as a surrogate for upper airway bacterial infections, in patients with symptomatic allergic rhinitis. Methods 14 patients with a history of moderate to severe pollen induced allergic rhinitis were challenged intranasally with LPS. After 3 to 6 weeks the same patients were challenged again, first with allergen and 24 hours later with LPS. Nasal symptom scores, nasal lavage leukocyte counts and nasal airway resistance were assessed at 6 and 24 h after each provocation along with measurements of nitric oxide (NO) levels in nose and lung. Results Six hours after the LPS challenge, increased level of leucocytes could be obtained in the lavage fluid, but no symptoms were experienced and no increase in nasal resistance could be recorded. The NO production in the upper and lower airways was similar before and 6 h after the provocation. In contrast, in patients exposed to pollen prior to the LPS challenge, both the nasal and the pulmonary NO levels were enhanced. This was accompanied by an increase in leukocytes. Conclusion The present study demonstrates a priming effect of allergen on the nasal response to LPS as well as the presence of a systemic link between airway mucosal sites in upper and lower airways. This suggests that exogenously derived signals, like upper airway infections, can interfere with the initiation, maintenance and progression of asthma.