Increased expression of IL-16 immunoreactivity in bronchial mucosa after segmental allergen challenge in patients with asthma

doi:10.1067/mai.2000.108112

Journal of Allergy and Clinical Immunology

Volume 106, Issue 2, August 2000, Pages 293-301

https://doi.org/10.1067/mai.2000.108112 Get rights and content

Abstract

Background: We have previously shown increased expression of the CD4⁺ cell chemoattractant IL-16 in bronchial mucosa of patients with asthma. We investigated the effects of allergen challenge on airway IL-16 expression. Methods: We investigated the expression of IL-16 immunoreactivity in bronchial biopsy samples obtained from atopic asthmatic subjects (n = 19) and normal subjects (n = 6) 24 hours after segmental allergen challenge. Control biopsy samples were obtained either at baseline or after diluent challenge. IL-16 expression was correlated to numbers of CD4⁺ cells, CD25⁺ cells, and activated eosinophils. IL-16 bioactivity was assessed in bronchoalveolar fluid obtained from patients with asthma. Results: IL-16 expression was higher in control biopsy specimens obtained from subjects with asthma compared with normal subjects (P < .05). In patients with asthma, numbers of IL-16 immunoreactive cells were significantly higher in biopsy specimens obtained after allergen challenge compared with control biopsy specimens (P < .001). Allergen provocation was associated with release of IL-16 in bronchoalveolar fluid in patients with asthma. In normal subjects, there was no difference in the number of IL-16–immunoreactive cells in biopsy specimens obtained after allergen challenge compared with biopsy specimens obtained after diluent challenge. Allergen challenge was associated with an increase in the numbers of EG2⁺ eosinophils in patients with asthma but not in normal subjects. IL-16 expression correlated with the numbers of CD4⁺ cells and CD25⁺ cells after allergen challenge in asthmatic subjects with a provocative concentration required to decrease the FEV₁ by 20% of its baseline value (PC₂₀FEV₁) < 4 mg/mL. IL-16–immunoreactive cells were identified mainly as T cells and eosinophils in asthmatic subjects after allergen challenge. Conclusion: Endobronchial allergen provocation in atopic asthmatic patients resulted in increased airway expression of IL-16 and release of bioactive IL-16 in airways. IL-16 may contribute to the immunoregulation of the inflammatory infiltrate in the airways in response to antigen. (J Allergy Clin Immunol 2000;106:293-301.)

Section snippets

Subjects

The study was approved by the Ethics Committee of The Royal Brompton and Harefield Hospitals NHS Trust, London, United Kingdom. The clinical characteristics of the study subjects are shown in Table I.

. Clinical characteristics of study population

Characteristic	Atopic asthmatic subjects	Normal control subjects
No.	18	6
Age (y)*	31.1 ± 7.5	22.4 ± 2.6
Sex (M/F)	8/10	6/0
Baseline FEV₁ (L)*	3.68 ± 0.84	4.43 ± 0.51
PC₂₀FEV₁ (mg/mL)*	3.59 ± 3.61	>32
Total IgE (IU/mL)*	319.1 ± 270.1†	85.0 ± 114.5
RAST to Der p or G	Positive

IL-16 immunoreactivity

At baseline, IL-16–immunoreactive cells were identified both in the epithelial and subepithelial areas. In normal subjects, the epithelial IL-16 immunoreactivity scores were low and score values did not differ in biopsy specimens obtained from the diluent-challenged and the allergen-challenged sites (Fig 1).

. Effects of allergen challenge on epithelial IL-16 immunoreactivity score in normal and asthmatic subjects. Asthmatic subjects were identified as subjects with either a PC₂₀FEV₁ value < 4

Discussion

The interaction of IL-16 and CD4⁺ cells may be of particular importance to asthma because IL-16 has the ability to selectively attract CD4⁺ cells in vitro through interaction with CD4. In this study, we used the technique of segmental allergen bronchoprovocation to investigate the role of IL-16 in the development of allergic inflammation. Our data show that specific allergen challenge was associated with an influx of inflammatory cells, particularly eosinophils. Increases in the numbers of both

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^☆: Supported by the Medical Research Council of Canada.

^☆☆: Sophie Laberge is a recipient of an MRC Scholarship, Canada. Qutayba Hamid is a Research Scholar of the Fonds de la Recherche en Santé du Québec.

^★: Reprint requests: Sophie Laberge, MD, Ste-Justine Hospital, 3175 Cote Ste-Catherine, Montreal, Quebec, H3T 1C5, Canada.

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Mechanisms of allergyIncreased expression of IL-16 immunoreactivity in bronchial mucosa after segmental allergen challenge in patients with asthma☆,☆☆,★

Abstract

Section snippets

Subjects

IL-16 immunoreactivity

Discussion

J Allergy Clin Immunol

Blood

J Allergy Clin Immunol

Lancet

Immunol Today

J Allergy Clin Immunol

J Allergy Clin Immunol

Mucosal inflammation in asthma

Am Rev Respir Dis

Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma

Am Rev Respir Dis

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

Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in brown-Norway rats

Immunology

CD4+ T cells can induce airway hyperresponsiveness to allergen challenge in the brown norway rat

Am J Resp Crit Care Med

Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ T cells in brown Norway rats

J Clin Invest

Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia

Am J Respir Cell Mol Biol

CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea

Am Rev Respir Dis

Mechanisms of allergy
Increased expression of IL-16 immunoreactivity in bronchial mucosa after segmental allergen challenge in patients with asthma☆,☆☆,★