Original Paper

Effect of Ciclesonide Treatment on Allergen-Induced Changes in T Cell Regulation in Asthma
Irene H. Heijink^{a, c}, Henk F. Kauffman^a, Edo Vellenga^c, Christa A. Veltman-Starkenburg^b, Dirkje S. Postma^b, Jan G.R. de Monchy^a

Departments of
^aAllergology,
^bPulmonary Diseases, and
^cHematology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

Address of Corresponding Author

Int Arch Allergy Immunol 2008;145:111-121 (DOI: 10.1159/000108136)

  Key Words

• Asthma allergic
• Corticosteroid
• Chemokine
• Th2 cells
• Adrenergic receptor

  Abstract

Background: The allergen-induced release of CCL17/thymus and activation-regulated chemokine (TARC) may be crucial in asthmatic airway inflammation by recruitment of Th2 cells. In addition, it might lead to aberrant Th2 cell activity through impairment of ₂-adrenergic receptor (₂-AR) control. We questioned how chemokine patterns change upon allergen challenge and whether treatment with the inhaled steroid ciclesonide can reduce chemokine release and subsequently prevent allergen-induced changes in Th2 cell regulation and migration. Methods: Asthma patients were double-blindly treated with placebo or 80 µg ciclesonide for 7 days. We studied allergen-induced changes in sputum chemokines, migration of peripheral blood T cells and control of ₂-agonist fenoterol over T cell migration and -CD3/-CD28-induced cytokine production. Results: Treatment with 80 µg ciclesonide significantly diminished the late asthmatic response. The late asthmatic response was associated with increased sputum levels of CCL17 and CCL4 (but none of the other chemokines measured) and loss of ₂-AR control over T cell migration and Th2-type cytokine production. Although ciclesonide treatment did not prevent chemokine release nor altered ₂-AR function in circulating T cells, it exerted an inhibitory effect on TARC-induced T cell migration and -CD3/-CD28-induced cytokine production. Conclusion: Our data support the hypothesis that CCL17 is involved in allergen-induced dysregulation of Th2 cell migration and cytokine production. Ciclesonide treatment inhibits T cell migration and cytokine production upon allergen inhalation, which is regulated independently from reducing CCL17 release, but may contribute to beneficial effects of ciclesonide on Th2-mediated airway inflammation.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Correspondence to: Dr. I.H. Heijink
Department of Allergology and Hematology
University Hospital Groningen, Hanzeplein 1
NL-9713 GZ Groningen (The Netherlands)
Tel. +31 50 361 9199, Fax +31 50 361 0570, E-Mail h.i.heijink@int.umcg.nl

  Article Information

Received: November 30, 2006
Accepted after revision: May 30, 2007
Published online: September 10, 2007
Number of Print Pages : 11
Number of Figures : 5, Number of Tables : 2, Number of References : 46