490
Allergic chronic sinusitis (ACS) and nonallergic
chronic sinusitis (NCS) are common causes of morbid-
ity and exert a significant impact on the health care sys-
tems of developed countries.
1
They are characterized by
inflammatory mucosal thickening and polyp formation
with a predominantly eosinophilic cellular infiltrate,
2
which is thought to be mediated by T cell–derived
cytokines.
Numerous in vitro studies support a role for Th-2
cytokines—IL-4, IL-5, and granulocyte-macrophage
colony-stimulating factor (GM-CSF)—in this eosino-
philia. We have recently shown that in allergic inflam-
mation there is increased local expression of IL-4,
3
which is essential for isotype switching in favor of IgE
Interleukin-4, interleukin-5, and granulocyte-macrophage
colony-stimulating factor receptor expression in chronic
sinusitis and response to topical steroids
ERIN D. WRIGHT, MD, SAUL FRENKIEL, MD, KHALID AL-GHAMDI, MD, OMAR GHAFFAR, BSc, PETER SMALL, MD, TONY TROUTT, PhD,
JAN TAVERNIER, PhD, and QUTAYBA HAMID, MD, PhD, Montreal, Canada, Seattle, Washington, and Ghent, Belgium
Chronic sinusitis and its associated eosinophilic infiltrate are believed to be mediated, at
least in part, by the upregulation of Th-2 cytokines, including interleukin-4, interleukin-5,
and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interleukin-4 is
involved in IgE production and in eosinophil recruitment through upregulation of vascular
cell adhesion molecule-1. Interleukin-5 and GM-CSF are involved in eosinophil growth and
survival. The aim of this study was to investigate the expression of receptors for these
cytokines in the sinus mucosa of subjects with chronic sinusitis. Using the technique of in
situ hybridization to detect specific cytokine receptor messenger RNA, we studied the sinus
mucosa of subjects with nonallergic chronic sinusitis, subjects with allergic chronic sinusi-
tis, subjects with allergic chronic sinusitis treated with topical steroids, and normal controls.
Our data demonstrate higher expression of interleukin-4 receptor in subjects with allergic
chronic sinusitis than in controls (p < 0.001) and higher expression of interleukin-5 receptor
in both subjects with nonallergic chronic sinusitis and subjects with allergic chronic sinusi-
tis than in controls (p < 0.001, p < 0.001). The expression of interleukin-4 receptor and inter-
leukin-5 receptor was higher in subjects with allergic chronic sinusitis than in subjects with
nonallergic chronic sinusitis (p < 0.001). GM-CSF receptor expression was also found to be
higher in subjects with allergic chronic sinusitis and subjects with nonallergic chronic
sinusitis than in controls (p < 0.001, p < 0.001). In contrast to interleukin-4 receptor and inter-
leukin-5 receptor, however, expression of GM-CSF receptor was higher in subjects with non-
allergic chronic sinusitis than in subjects with allergic chronic sinusitis (p < 0.001). In sub-
jects with allergic chronic sinusitis treated with topical corticosteroids, the expression of
interleukin-4 receptor and interleukin-5 receptor messenger RNA levels was significantly
lower than levels in patients with allergic chronic sinusitis who were not taking topical
steroids (p < 0.001, p < 0.001). Steroid treatment had no effect on GM-CSF receptor mes-
senger RNA expression. In conclusion, our data support a role for Th-2 cytokine receptors
in the pathophysiology of chronic sinusitis. Further, our data lend support to the theory that
differential activation of distinct cytokine pathways mediates inflammation in chronic
sinusitis depending on whether there is associated allergy. Finally, treatment with topical
corticosteroids has been demonstrated in chronic sinusitis to downregulate receptors for
interleukin-4 and interleukin-5. (Otolaryngol Head Neck Surg 1998;118:490-5.)
From Meakins-Christie Laboratories (Drs. Wright, Al-Ghamdi, and
Hamid and Mr. Ghaffar); McGill Nasal Research Group (Drs.
Frenkiel, Small, and Hamid); the SMBD-Jewish General Hospital,
McGill University, Montreal (Drs. Wright, Frenkiel, Al-Ghamdi,
and Small); the Immunex Corp. (Dr. Troutt); and the Department of
Biochemistry, University of Ghent, Belgium (Dr. Tavernier).
Supported by the Network Center of Excellence for Respiratory
Diseases and MRC, Canada.
Recipient of the Sam Sanders Award for Best Paper in Basic Science
at the Annual Meeting of the American Academy of Otolaryngic
Allergy, Washington, D.C., Sept. 26-28, 1996.
Reprint requests: Qutayba Hamid, MD, PhD, Meakins-Christie
Laboratories, 3626 St. Urbain St., Montreal, Quebec, H2X 2P2,
Canada.
Copyright © 1998 by the American Academy of Otolaryngology–
Head and Neck Surgery Foundation, Inc.
0194-5998/98/$5.00 + 0 23/1/80537