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Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation

Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation
Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation
Allergic mucosal inflammation is characterized by the presence of cell infiltration, predominantly with IgE-sensitized mast cells and activated eosinophils, and appears to be regulated by the local production and release of several cytokines, particularly IL-4 and IL-5. Although attention has focused on the Th2 subpopulation of CD4+ T lymphocytes as an important source of these cytokines, human mast cells have been shown to both store and secrete IL-4 and TNF-alpha. To investigate the expression of cytokines relevant to allergic inflammation and to identify their cellular localization within the nasal mucosa, we have undertaken specific immunohistochemical staining of thin sections of inferior turbinate biopsies from patients with perennial allergic rhinitis and, for comparison, from nonatopic healthy volunteers. The cytokines investigated were IL-4, IL-5, IL-6, and IL-8. In both the normal and rhinitic biopsies numerous cells immunoreactive for IL-4, IL-5, and IL-6 were seen. Staining of adjacent 2-microns sections for CD3, mast cell tryptase, and eosinophil cationic protein revealed that 90% of the IL-4 immunoreactive cells were mast cells, with biopsies from rhinitic subjects containing significantly more IL-4+ cells than biopsies from normal controls (p = 0.02), especially when assessed with the anti-IL-4 mAb 3H4. Mast cells also accounted for > 90% of IL-6 and > 50% of IL-5 immunoreactive cells. IL-5 immunoreactivity was also localized to eosinophils, whereas IL-8 localized predominantly to the nasal epithelium in both groups. No cytokines were found in association with T lymphocytes. These findings indicate that the mast cell is an important source of preformed cytokines and as such may contribute to the chronicity of the mucosal inflammation that characterizes allergic rhinitis.
0022-1767
3853-3865
Bradding, P.
39990c99-3c21-44b6-b1f7-084eddf29722
Feather, I.H.
85baeb57-711f-4ac1-91dc-1f6949170dfe
Wilson, S.J.
21c6875d-6870-441b-ae7a-603562a646b8
Bardin, P.G.
92b18c26-9432-4605-954d-85e6d3f1cdbe
Heusser, C.H.
417f2604-5311-4498-b726-8da30e22f575
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Howarth, P.H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Bradding, P.
39990c99-3c21-44b6-b1f7-084eddf29722
Feather, I.H.
85baeb57-711f-4ac1-91dc-1f6949170dfe
Wilson, S.J.
21c6875d-6870-441b-ae7a-603562a646b8
Bardin, P.G.
92b18c26-9432-4605-954d-85e6d3f1cdbe
Heusser, C.H.
417f2604-5311-4498-b726-8da30e22f575
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Howarth, P.H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21

Bradding, P., Feather, I.H., Wilson, S.J., Bardin, P.G., Heusser, C.H., Holgate, S.T. and Howarth, P.H. (1993) Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation. Journal of Immunology, 151 (7), 3853-3865. (PMID:8376806)

Record type: Article

Abstract

Allergic mucosal inflammation is characterized by the presence of cell infiltration, predominantly with IgE-sensitized mast cells and activated eosinophils, and appears to be regulated by the local production and release of several cytokines, particularly IL-4 and IL-5. Although attention has focused on the Th2 subpopulation of CD4+ T lymphocytes as an important source of these cytokines, human mast cells have been shown to both store and secrete IL-4 and TNF-alpha. To investigate the expression of cytokines relevant to allergic inflammation and to identify their cellular localization within the nasal mucosa, we have undertaken specific immunohistochemical staining of thin sections of inferior turbinate biopsies from patients with perennial allergic rhinitis and, for comparison, from nonatopic healthy volunteers. The cytokines investigated were IL-4, IL-5, IL-6, and IL-8. In both the normal and rhinitic biopsies numerous cells immunoreactive for IL-4, IL-5, and IL-6 were seen. Staining of adjacent 2-microns sections for CD3, mast cell tryptase, and eosinophil cationic protein revealed that 90% of the IL-4 immunoreactive cells were mast cells, with biopsies from rhinitic subjects containing significantly more IL-4+ cells than biopsies from normal controls (p = 0.02), especially when assessed with the anti-IL-4 mAb 3H4. Mast cells also accounted for > 90% of IL-6 and > 50% of IL-5 immunoreactive cells. IL-5 immunoreactivity was also localized to eosinophils, whereas IL-8 localized predominantly to the nasal epithelium in both groups. No cytokines were found in association with T lymphocytes. These findings indicate that the mast cell is an important source of preformed cytokines and as such may contribute to the chronicity of the mucosal inflammation that characterizes allergic rhinitis.

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Published date: 1 October 1993

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Local EPrints ID: 191019
URI: https://eprints.soton.ac.uk/id/eprint/191019
ISSN: 0022-1767
PURE UUID: b31b50e0-f329-4a2a-93d7-58f3676dddaf

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Date deposited: 20 Jun 2011 15:36
Last modified: 28 Jun 2018 16:31

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