Evidence for distinct cytokine expression in allergic versus nonallergic chronic sinusitis,☆☆,

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Abstract

Background: The purpose of this study was to characterize the relationship between tissue cytokine expression and the cellular infiltrate present in chronic hyperplastic sinusitis with nasal polyposis (CHS/NP) and to compare the immunopathology and cytokine profile of patients with allergy versus patients without allergy. Methods: Nasal polyp tissue samples from 12 patients with CHS/NP and nasal turbinate biopsy specimens from 10 normal control patients were examined for the expression of interleukin (IL)-4, IL-2, and interferon (IFN)-γ cytokine messenger RNA (mRNA) species by in situ hybridization. These data were analyzed in conjunction with data previously reported for the cytokine mRNA species granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-5 and the immunocytochemical profile of the inflammatory cell infiltrate. Patients with allergy were distinguished from those without allergy on the basis of allergy skin tests. Results: Tissue eosinophilia was a prominent feature of both allergic and nonallergic CHS/NP and correlated in both subgroups with the density of GM-CSF and IL-3 mRNA+ cells. In comparison with normal controls, patients with allergic CHS/NP had significantly higher tissue densities of GM-CSF, IL-3, IL-4, and IL-5 (p ≤ 0.025). In contrast, patients with nonallergic CHS/NP had significantly higher tissue densities of GM-CSF, IL-3, and IFN-γ (p ≤ 0.001). The allergic and nonallergic subgroups showed distinct cytokine profiles with the most distinguishing cytokines of the allergic subgroup being IL-4 (p = 0.001) and IL-5 (p = 0.017) and of the nonallergic subgroup being IFN-γ (p = 0.004). Furthermore, patients with allergic CHS/NP showed an increased density of CD3+ T lymphocytes compared with either controls or patients with nonallergic CHS/NP (p = 0.03). The density of CD3+ T lymphocytes was the only significant difference between patients with allergic and nonallergic CHS/NP. A clinical history of aspirin sensitivity was strongly correlated with nonallergic CHS/NP, as well as the nonallergic CHS/NP profile of cytokines, including IFN-γ. Conclusion: We conclude that distinct mechanisms of eosinophilia exist in patients with allergic versus nonallergic CHS/NP. The allergic mechanism involves production of TH2-type cytokines, including GM-CSF, IL-3, IL-4, and IL-5, by infiltrating T lymphocytes. The nonallergic mechanism remains unknown but does involve production of GM-CSF, IL-3, and IFN-γ. However, nonallergic eosinophilia is independent of IL-4 and IL-5, cytokines that contribute to tissue eosinophilia in allergic inflammation. Aspirin sensitivity is strongly correlated with nonallergic CHS/NP and production of the nonallergic CHS/NP profile of cytokines, including IFN-γ. (J Allergy Clin Immunol 1995;96:537-44.)

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Patient selection

The patient selection process, clinical characteristics, and sinus and allergic evaluation for CHS/NP have been previously reported.3 All were adult patients (age range, 18 to 50 years, n = 12) at the National Jewish Center for Immunology and Respiratory Medicine and were selected on the basis of a history of more than 1 year of chronic perennial sinusitis with one or more of the following symptoms: chronic perennial nasal congestion, chronic rhinorrhea, chronic postnasal drip, anosmia,

Densities of EG2+ eosinophils

The CHS/NP patients were subdivided into an allergic subgroup (n = 5) and a nonallergic subgroup (n = 7) on the basis of the results of allergy skin testing. Both the allergic and nonallergic subgroups of patients with CHS/NP had greater densities of EG2+ eosinophils than controls (p = 0.0005 and 0.001 for allergic and nonallergic CHS/NP versus controls, respectively) as shown in Fig. 1, and in both subgroups this increased density was associated with increased GM-CSF and IL-3 (Fig. 2).

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DISCUSSION

In this study, we have demonstrated distinct tissue cytokine expression in patients with allergic versus nonallergic CHS/NP. In both allergic and nonallergic CHS/NP, patients showed increased tissue densities of GM-CSF and IL-3 mRNA+ cells. The expression of these two cytokines correlated strongly with the density of tissue eosinophils in patients with allergic and with nonallergic CHS/NP. It has been previously reported that activated eosinophils produce a variety of cytokines, including both

Acknowledgements

We thank Drs. Barry P. Berlin and Nigel Pashley for assisting in subject recruitment and specimen collection. We also thank Ms. Kristen Moore and Mrs. Phyllis Siracusano for expert preparation of the manuscript and Glaxo Biogen (Geneva) for supplying the cytokine probes.

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    From athe Departments of Medicine and Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, and the Department of Ear, Nose and Throat Surgery, University of Colorado Health Sciences Center, Denver; and bthe Departments of Medicine and Pathology, McGill University, Meakins-Christie Laboratories, Montreal.

    ☆☆

    Supported by grants from the Clinical Investigation Committee of National Jewish Center for Immunology and Respiratory Medicine, National Institutes of Health Grants AR41256, HL37260, and RR00051, the Montreal Chest Research Institute, and the J.T. Costello Memorial Research Fund.

    Reprint requests: Daniel L. Hamilos, MD, Washington University School of Medicine, Box 8122, 660 S. Euclid Ave., St. Louis, MO 63110.

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