Influence of interleukin-8 challenge in the nasal mucosa in atopic and nonatopic subjects.
Interleukin-8 (IL-8) is a major cytokine in the recruitment of neutrophils (polymorphonuclear leukocytes) to areas of inflammation. It also activates T lymphocytes and cytokine-primed basophils and eosinophils and therefore may be implicated as an effector in allergic inflammation. IL-8 has also been identified as a mediator in such inflammatory pulmonary conditions as cystic fibrosis, allergen challenge, and sarcoidosis. To investigate the bioactivity of IL-8 in humans, we examined the effects of nasal challenge with human recombinant IL-8 in a double-blind placebo-controlled crossover study in which nasal resistance and rhinitic symptoms were monitored for 4 h after challenge. Cellular infiltration was quantified on differentially stained nasal smears obtained at hourly intervals. Cellular responses caused by in vivo priming were assessed by a comparison of atopic and nonatopic patient groups. A significant neutrophilic infiltrate in smear samples was observed in all patients challenged with IL-8 from 12 +/- 4% (mean +/- SEM) at baseline to 60 +/- 6% after 4 h; placebo challenge resulted in an increase in neutrophils to 30 +/- 4% (p < 0.04). Additionally, a significant increase in cumulative eosinophil recruitment occurred over the challenge period. Nasal resistance was significantly increased 10 min after instillation of IL-8 in all subjects compared with placebo, but there was no difference between atopic and nonatopic subjects. Nasal rhinitic symptoms were also increased in all subjects receiving IL-8 compared with placebo. In a further study in 19 subjects, nasal biopsy was performed 3 h after IL-8 or placebo challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Douglass
J A
JA
Immunopharmacology Group, University Medicine, Southampton General Hospital, England.
Dhami
D
D
Gurr
C E
CE
Bulpitt
M
M
Shute
J K
JK
Howarth
P H
PH
Lindley
I J
IJ
Church
M K
MK
Holgate
S T
ST
D000293:Adolescent; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001706:Biopsy; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis* / Q000453:epidemiology; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009299:Nasal Provocation Tests / Q000379:methods / Q000706:statistics & numerical data; D011994:Recombinant Proteins / Q000008:administration & dosage; D012220:Rhinitis / Q000175:diagnosis* / Q000453:epidemiology; D018709:Statistics, Nonparametric; D013997:Time Factors
D016209:Interleukin-8; D011994:Recombinant Proteins