Effect of intranasal challenge with interleukin-6 on upper airway symptomatology and physiology in allergic and nonallergic patients

Background: Interleukin-6 (IL-6) is a potent regulator of airway inflammati on and an important component of biologic homeostasis. Previously, a tempor al relationship between the local elaboration of IL-6 and the development o f upper airway symptoms and pathophysiologic findings was reported for pati ents experimentally infected with influenza A virus or rhinovirus. Objective: The objective of this study was to determine the provocative eff ects of direct, intranasal administration of IL-6 on those symptoms, signs, and pathophysiologic findings that accompany viral upper respiratory infec tion. Methods: In this double-blind, placebo-controlled, crossover trial, 10 symp tomatic allergic, 10 asymptomatic allergic, and 10 nonallergic adult patien ts were pretreated with intranasal histamine and, after 15 minutes, were ch allenged with repeated doses of placebo (saline) or with increasing doses ( 0, 0.01, 0.1, and 1 mug/mL) of recombinant IL-6 at 20-minute intervals, dur ing randomized paired sessions. Symptom scores, sneeze and cough counts, na sal secretion weights, nasal conductance (rhinomanometry), middle ear press ure (tympanometry), Eustachian tube function (sonotubometry), and pulmonary function (spirometry) were evaluated before and after the histamine challe nge, after each dose of IL-6 or placebo, and then at 90 minutes and 2, 3, 4 , 6, and 24 hours. Results: At the doses used, intranasal challenge with IL-6 wits well tolera ted. At the 90-minute postchallenge endpoint, a significant effect of chall enge substance and group assignment was documented for nasal secretion weig ht. Paired comparisons showed that the effect was greater for the allergic patients when compared with the nonallergic patients. There were no differe nces between placebo and IL-6 challenge for any of the other measured param eters. Conclusions: These results show that local IL-6 at relatively low doses can provoke increased nasal secretions in patients with allergic rhinitis.