Da. Gentile et al., Effect of intranasal challenge with interleukin-6 on upper airway symptomatology and physiology in allergic and nonallergic patients, ANN ALLER A, 86(5), 2001, pp. 531-536
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.