Effect of ciclesonide treatment on allergen-induced changes in T cell regulation in asthma.

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 beta2-adrenergic receptor (beta2-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 microg ciclesonide for 7 days. We studied allergen-induced changes in sputum chemokines, migration of peripheral blood T cells and control of beta2-agonist fenoterol over T cell migration and alpha-CD3/alpha-CD28-induced cytokine production.

RESULTS:

Treatment with 80 microg 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 beta2-AR control over T cell migration and Th2-type cytokine production. Although ciclesonide treatment did not prevent chemokine release nor altered beta2-AR function in circulating T cells, it exerted an inhibitory effect on TARC-induced T cell migration and alpha-CD3/alpha-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.

• Authors: Irene H Heijink, Henk F Kauffman, Edo Vellenga, Christa A Veltman-Starkenburg, Dirkje S Postma, Jan G R de Monchy
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 145 Issue 2 Pg. 111-21 ( 2008) ISSN: 1423-0097 [Electronic] Switzerland
• PMID: 17848804 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: 2007 S. Karger AG, Basel

Chemical References

• Allergens
• Anti-Asthmatic Agents
• Arrestins
• CCL17 protein, human
• CCL4 protein, human
• Chemokine CCL17
• Chemokine CCL4
• Cytokines
• Pregnenediones
• Receptors, Adrenergic, beta-2
• beta-Arrestins
• Fenoterol
• ciclesonide

Topics

• Adolescent
• Adult
• Allergens (immunology)
• Anti-Asthmatic Agents (pharmacology, therapeutic use)
• Arrestins (analysis)
• Asthma (drug therapy, immunology)
• Cell Movement (drug effects)
• Chemokine CCL17 (metabolism)
• Chemokine CCL4 (analysis)
• Cytokines (pharmacology)
• Double-Blind Method
• Female
• Fenoterol (pharmacology, therapeutic use)
• Humans
• Male
• Middle Aged
• Pregnenediones (pharmacology, therapeutic use)
• Receptors, Adrenergic, beta-2 (immunology)
• Sputum (chemistry)
• T-Lymphocyte Subsets (immunology)
• Th2 Cells (drug effects, immunology)
• beta-Arrestins