Immunomodulative function of Azithromycin on asthmatic children.—Emphasis on Th1/Th2 cells , T cell apoptosis and dendritic cell funtion

Asthma is a chronic inflammatory disease characterized by airway inflammation that are largely mediated by type 2 helper T (Th2) cells, eosinophils and mast cells, which could be controlled by inhaled corticosteroid. Azithromycin (AZM) is widely used in pediatric respiratory tract infections, particularly against Mycoplasma pneumonia. Clinical experience has shown that in addition to bacteriocidal effect, azithromycin possesses intrinsic anti-inflammatory effect, providing another therapeutic benefit for asthmatic children. Our project aims to examine the immunomodulative effect of azithromycin on adaptive immunity in asthmatic children. During the first year, we will examine the anti-inflammatory effects of AZM on cytokine profiles of activated CD4+ T cells (Th0), Th1-biased cells (Th1), and Th2-biased cells (Th2) from both atopic asthmatic children as well as non-atopic controls. Our lab and others have shown that AZM also induced apoptosis in anti-CD3/CD28 activated T cells. It would be of interest to know whether the apoptosis of Th1 and Th2 cells are affected by AZM differentially. Our second year effort will focus on investigating the susceptibility to Fas-mediated and TNF-α-induced apoptosis of Th2 cells. We will detail the kinetics of Fas- and TNF-α-mediated apoptosis and caspase 3 expression along with regulatory effect of AZM. Dendritic cells (DCs) play a central role in the initiation and maintenance of allergic status. Corticosteroids were found to significantly affect DCs. Our third year work will be dedicated to compare the immunomodulative effect of AZM on DC from asthmatic subject with that of steroids. We would also seek to determine the synergistic effect of steroid and azithromycin on DC function. These studies will provide insight for AZM as a potential steroid-sparing asthma therapeutic option.

Project ID:PC10001-0106
External Project ID:NSC98-2314-B182A-093-MY3