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 inflammation and an important component of biologic homeostasis. Previously, a temporal relationship between the local elaboration of IL-6 and the development of upper airway symptoms and pathophysiologic findings was reported for patients experimentally infected with influenza A virus or rhinovirus.


OBJECTIVE
The objective of this study was to determine the provocative effects of direct, intranasal administration of IL-6 on those symptoms, signs, and pathophysiologic findings that accompany viral upper respiratory infection.


METHODS
In this double-blind, placebo-controlled, crossover trial, 10 symptomatic allergic, 10 asymptomatic allergic, and 10 nonallergic adult patients were pretreated with intranasal histamine and, after 15 minutes, were challenged with repeated doses of placebo (saline) or with increasing doses (0, 0.01, 0.1, and 1 microg/mL) of recombinant IL-6 at 20-minute intervals, during randomized paired sessions. Symptom scores, sneeze and cough counts, nasal secretion weights, nasal conductance (rhinomanometry), middle ear pressure (tympanometry), Eustachian tube function (sonotubometry), and pulmonary function (spirometry) were evaluated before and after the histamine challenge, 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 was well tolerated. At the 90-minute postchallenge endpoint, a significant effect of challenge substance and group assignment was documented for nasal secretion weight. Paired comparisons showed that the effect was greater for the allergic patients when compared with the nonallergic patients. There were no differences between placebo and IL-6 challenge for any of the other measured parameters.


CONCLUSIONS
These results show that local IL-6 at relatively low doses can provoke increased nasal secretions in patients with allergic rhinitis.
Gentile
D A
DA
Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA. gentild@chplink.chp.edu
Yokitis
J
J
Angelini
B L
BL
Doyle
W J
WJ
Skoner
D P
DP
D000158:Acoustic Impedance Tests; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D003371:Cough / Q000139:chemically induced; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005064:Eustachian Tube / Q000503:physiopathology; D005260:Female; D006632:Histamine; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D009299:Nasal Provocation Tests; D010865:Pilot Projects; D011994:Recombinant Proteins; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D012137:Respiratory System / Q000187:drug effects*; D012882:Skin Tests; D012912:Sneezing; D013147:Spirometry
D015850:Interleukin-6; D011994:Recombinant Proteins; D006632:Histamine