The time course of the bilateral release of cytokines and mediators after unilateral nasal allergen challenge

Abstract

Late phase reactions after allergen challenge can be understood as a correlate of the inflammatory reaction in allergic rhinitis. To investigate which cytokines are involved in it and to dissect direct and indirect effects of nasal allergen challenge, we performed unilateral nasal allergen provocation with the disc method in 12 seasonal allergic volunteers. Symptom scores, nasal secretions and nasal airflow were quantified. In the secretions that were collected in the early phase and for 8 h after provocation, we measured histamine, and the cytokines interleukin (IL)-1beta, IL-8, IL-4, and the natural antagonist of IL-1beta, IL-1 receptor type 1 (IL-1Ra) using enzyme-linked immunosorbent (ELISA)-assays. Control challenges with diluent instead of allergen were performed in all subjects. We demonstrated a bilateral increase in nasal secretion weights in the early and late phase. Histamine was significantly increased in the early and late phase in nasal secretions from both nostrils. IL-1beta increased in the late phase only, where it was also found on the unchallenged, contralateral side. Its antagonist IL-1Ra was found in very high quantities (1000-fold higher than IL-1beta) but demonstrated only marginal changes after provocation. IL-8 was increased in both nostrils early and late after challenge, whereas IL-4 was significantly elevated in the late phase. We described the time course of mediator and cytokine release into nasal secretions after allergen challenge. We hypothesize that the observed indirect effects on the unchallenged, contralateral side can be at least partially attributed to neuronal reflexes.