Abstract:

Background: 

Asthma exacerbations represent the main source of costs and morbidity in asthma care, and drugs specifically designed to prevent exacerbations are needed. A prerequisite is to dispose of a precise knowledge of inflammatory events leading to exacerbations. Objective: 

To study T-cell activation during exacerbations from severe refractory asthmatics. Methods: 

Proportions of blood T-cell interleukin (IL)-13, interferon-γ, IL-4, IL-5, IL-10 production and of CD4+CD25+^highCD62L+CD45RO+ [T regulatory (Treg)] cells were determined by flow cytometry. Blood cytokine mRNA was studied by reverse transcription-polymerase chain reaction and the respective protein levels were determined by cytokine beads array. Depletion of Treg cells was performed to study their activation. T-cell cytokines were detected in parallel in induced sputum. Results: 

At baseline, T helper 2 (Th2) cells were increased in asthmatics, whereas T helper 1 (Th1) and Treg T cells were decreased. T helper 2 cells increased before exacerbations, followed by Th1 cells, in blood and induced sputum, albeit Treg cells decreased in parallel with IL-10-producing T cells. Concordant results were found at the mRNA level. The suppressive activity of Treg cells was impaired during exacerbations compared to baseline. Conclusions: 

New insights are given into pathophysiology of asthma exacerbations: Although at baseline T-cell activation is Th2-biased, a mixed Th1/Th2 activation occurs during exacerbations. The Treg cell deficiency found at baseline in SRA increases during exacerbations.

Keywords: asthma; T helper 1 cells; T helper 2 cells; T-regulatory cells

Document Type: Research article

DOI: 10.1111/j.1398-9995.2008.01687.x

Affiliations: 1: Université de la Méditerranée, EA 3287, IFR125 2: Assistance Publique - Hôpitaux de Marseille, Fédération Médico-chirurgicale de Pathologie Respiratoire et Thoracique 3: Laboratoire Central, Assistance Publique - Hôpitaux de Marseille 4: Centre d'Investigations Cliniques, INSERM, Assistance Publique - Hôpitaux de Marseille, Department-EA 3287 Marseilles, France