Intranasal steroids decrease eosinophils but not mucin expression in
P-R. Burgel*, L.O. Cardell#, I.F. Ueki}, J.A. Nadel}
Intranasal steroids decrease eosinophils but not mucin expression in nasal polyps.
P-R. Burgel, L.O. Cardell, I.F. Ueki, J.A. Nadel. #ERS Journals Ltd 2004.
ABSTRACT: Increased mucin expression is a feature of nasal polyposis. Cortico-
steroids reduce polyp size and symptoms, but their effect on mucin production remains
unknown. In this study, the effects of intranasal corticosteroids on MUC5AC mucin
expression, nasal resistance, eosinophil and neutrophil infiltration, epidermal growth
factor receptor (EGFR), interleukin (IL)-8, and tumour necrosis factor (TNF)-a
expression was assessed in nasal polyps.
In nine subjects, one nasal polyp was removed surgically before treatment and
another was removed after 8 weeks of intranasal fluticasone (400 mg?day-1). Tissues
were processed for in situ hybridisation and immunohistochemical staining. Described
effects of fluticasone on nasal polyps (reduction in nasal resistance and in eosinophil
infiltration) were evaluated. Morphometric analysis was performed to assess the effect
of fluticasone on epithelial-, MUC5AC-, EGFR- and IL-8-stained areas, TNF-a-
stained cells, and neutrophil numbers.
Treatment with fluticasone decreased nasal resistance and intra-epithelial eosino-
phils. The MUC5AC-stained area in the epithelium was unchanged by treatment;
MUC5AC mRNA expression was unaffected by treatment. EGFR-stained area, intra-
epithelial neutrophil numbers, IL-8 and TNF-a expression were also unchanged by
Intranasal fluticasone was effective in decreasing nasal airflow resistance and intra-
epithelial eosinophils but had no effect on mucin or epidermal growth factor receptor
expression or on neutrophil recruitment.
Eur Respir J 2004; 24: 594–600.
*Service de Pneumologie, Universite ´ Rene ´
Descartes, Ho ˆpital Cochin, Paris, France.
#Dept of Otorhinolaryngology, Malmo ¨ Uni-
versity Hospital, Malmo ¨, Sweden.
vascular Research Institute, and Dept of
Medicine and Physiology, University of Cali-
fornia, San Francisco, CA, USA.
Correspondence: J.A. Nadel, Cardiovascular
Research Institute, Box 0130, University of
California San Francisco, San Francisco, CA
94 143-0130, USA.
Fax: 01 4154762283
Keywords: Airway epithelium
epidermal growth factor receptor
Received: February 4 2004
Accepted after revision: May 4 2004
This work was funded by private funds. P-R.
Burgel is a recipient of a grant from "Colle `ge
des Professeurs de Pneumologie".
Goblet cell hyperplasia and increased mucin expression
are features of nasal polyp epithelium , but, currently, no
effective therapy for mucus hypersecretion is established.
Eosinophil infiltration is a characteristic finding in nasal
polyp tissue. Neutrophils are recruited into the airways in
hypersecretory airway diseases (e.g. chronic obstructive
pulmonary disease, cystic fibrosis, bronchiectasis, acute asthma)
and are also found in nasal polyps . Neutrophil chemoat-
tractants are upregulated in the airways of these diseases 
and expression of the neutrophil chemoattractant interleukin
(IL)-8 is reported in nasal polyp tissue . Several neutrophil
products are reported to play important roles in mucin
production, including oxygen free radicals  and elastase .
Eosinophil products also increase mucin production in airway
epithelial cells . Therefore, both eosinophils and neutro-
phils have been suspected to play roles in the increased mucin
expression found in nasal polyps .
Corticosteroids are the recommended medical therapy
for nasal polyps. They are effective in decreasing the size of
polyps [8, 9] and in inhibiting eosinophil infiltration into
polyp tissue , but their effect on mucin production is not
Several mucins are expressed in human airways. Among
these mucins, gel-forming mucins found in airway secretions
include MUC2, MUC5AC and MUC5B. MUC2 expression
has not been found consistently in immunohistochemical
studies  and only a small amount of MUC2 protein has
been found in airway secretions . Although MUC5B is
reported to be expressed in goblet cells in normal nasal
epithelium, it is believed to be localised preferentially to
airway submucosal glands . Furthermore, there appear to
be no reports of MUC5B protein expression in nasal polyps.
In contrast, MUC5AC is consistently reported to be expres-
sed in both nasal and lower airway epithelium [1, 11]. We
have previously shown that MUC5AC gene and protein
are expressed in nasal polyp epithelium, and that MUC5AC-
stained area in nasal polyp epithelium is comparable to AB/
PAS-stained area . Because both epidermal growth factor
receptor (EGFR) activation  and leukocyte products have
been implicated in mucin production, the effects of intranasal
fluticasone on mucin MUC5AC and EGFR expression, and
on leukocyte infiltration were examined in this study.
In each subject, one polyp was removed before cortico-
steroid therapy and a second polyp was removed after 8 weeks
of treatment with an intranasal corticosteroid, fluticasone.
The effectiveness of fluticasone on the size of polyps (evalu-
ated by nasal airflow resistance) and eosinophil numbers was
assessed, both of which are known to be decreased by flutica-
sone . To assess the effect of fluticasone on mucin produc-
tion and its effect on the EGFR cascade, in situ hybridisation
and immunohistochemistry for MUC5AC gene, and protein
expression and immunohistochemistry for EGFR protein
Eur Respir J 2004; 24: 594–600
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European Respiratory Journal
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