Detection of Cytokines and Their Cell Sources in Bronchial Biopsy Specimens From Asthmatic Patients: Relationship to Atopic Status, Symptoms, and Level of Airway Hyperresponsiveness

doi:10.1378/chest.105.3.687

Chest

Volume 105, Issue 3, March 1994, Pages 687-696

https://doi.org/10.1378/chest.105.3.687 Get rights and content

This study evaluated immunoreactivity for several cytokines in bronchial tissue of asthmatic patients and related this to the clinical and functional characteristics. Patients were allocated into two different groups on the basis of their atopic status (atopic and nonatopic), with two subgroups of symptomatic and asymptomatic subjects in each. Five healthy volunteers were tested as control subjects. After clinical and functional assessment, all of the subjects underwent bronchoscopy. Several biopsy specimens were obtained for immunohistochemical and immunoelectron microscopic evaluation. Symptomatic asthmatic subjects had increased expression of immunoreactive interleukin (IL) 1β IL-2, IL-3, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor a (TNFα) when compared to the asymptomatic patients or normal control subjects. The cell sources of IL-1β were monocytes and dendritic cells in atopic patients and monocytes alone in nonatopic asthmatic subjects. The CD4+ T lymphocytes from atopic asthmatic subjects predominantly expressed IL-3, IL-4, IL-5, and GM-CSF immunoreactivity, whereas CD4+ T cells from nonatopic patients predominantly expressed IL-2, IL-3, and IL-5, and GM-CSF immunoreactivity. Mast cells showed immunoreactivity for TNFα, IL-3, IL-5, and GM-CSF. Immunostaining for TNFα and GM-CSF was also detected in bronchial epithelial cells and monocytes. Tissue eosinophilia and the level of airway hyperresponsiveness more closely correlated with IL-5 immunoreactivity in atopic asthmatic subjects and with IL-2 and GM-CSF immunoreactivity in nonatopic patients.

Section snippets

Subjects and Study Design

Thirty-three nonsmokers were selected for this study (11 women; mean age, 32 years [range, 18 to 45 years]). They were recruited among the patients of the Diagnostic Center for Respiratory and Allergic Diseases and from asthmatic subjects or healthy volunteers responding to advertisements. Twenty-eight subjects had a history of allergic or nonallergic asthma lasting for 2 years or longer. Five were healthy control subjects with no history of asthma or atopic diseases and with negative skin

Functional Assessment

Atopic and nonatopic asthmatic subjects were allocated into two distinct subgroups on the basis of symptom scores (Table 1). Asymptomatic patients were free of symptoms during the monitoring period and did not receive any medication. Patients with current symptoms of asthma had spontaneous airflow obstruction, as demonstrated by the diurnal and day-to-day variability of PEFR, and had higher levels of airway responsiveness to inhaled metha-choline than asymptomatic subjects (Table 1).

Immunohistochemistry and Immunoelectron Microscopy

Symptomatic

DISCUSSION

In our study, we confirm and extend previous observations indicating that the bronchial mucosa of asthmatic patients is infiltrated with increased numbers of activated eosinophils and T lymphocytes1, 2, 3, 4, 5, 6, 7,¹²,¹³ and that this occurs both in atopic and nonatopic patients.⁶,⁷ Infiltration of eosinophils and their activation may contribute to airflow obstruction and functional derangement, because the number of activated eosinophils was higher in asthmatic subjects with current symptoms

ACKNOWLEDGMENT

We thank all of the subjects who volunteered to participate in this study, S. Moretti for laboratory assistance, and A. Grossi for typing the manuscript.

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: Supported by funds from the National Research Council, the Italian Association for Cancer Research, and CARIPLO.

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Chest

Clinical Investigations: Asthma/BronchodilatorsDetection of Cytokines and Their Cell Sources in Bronchial Biopsy Specimens From Asthmatic Patients: Relationship to Atopic Status, Symptoms, and Level of Airway Hyperresponsiveness

Section snippets

Subjects and Study Design

Functional Assessment

Immunohistochemistry and Immunoelectron Microscopy

DISCUSSION

ACKNOWLEDGMENT

J Allergy Clin Immunol

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

J Invest Dermatol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

The pathology of asthma with special reference to change in the bronchial mucosa

J Clin Pathol

Bronchial biopsy in chronic bronchitis and asthma

Thorax

Some histological changes in chronic bronchitis and asthma

Thorax

A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis, and in emphysema

Thorax

Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma: relationship to bronchial hyperresponsivity

Am Rev Respir Dis

Human eosinophil major basic protein induces airway constriction and airway hyperresponsiveness in primates

J Clin Invest

T cell subsets and their soluble products regulate eosinophilia in allergic and non-allergic asthma

J Immunol

Expression of mRNA for interleukin 5 in mucosal bronchial biopsies from asthma

J Clin Invest

Predominant Th2-like bronchoalveolar T lymphocyte population in atopic asthma

N Engl J Med

TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties

Ann Rev Immunol

Recombinant human interleukin-5 is a selective activator of human eosinophil function

J Exp Med

Clinical Investigations: Asthma/Bronchodilators
Detection of Cytokines and Their Cell Sources in Bronchial Biopsy Specimens From Asthmatic Patients: Relationship to Atopic Status, Symptoms, and Level of Airway Hyperresponsiveness