The effects of azithromycin on cell growth and cytokine gene expression of T helper cells

• Main Authors: Wan Jung Lee, 李宛蓉
• Other Authors: Ming Lin Kuo
• Format: Others
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/07672534301040558007

碩士 === 長庚大學 === 生物醫學研究所 === 97 === Asthma is a chronic pulmonary inflammatory disorder. The disease is characterized by infiltration of many inflammation cells, including mast cells, eosinophils and activated-T lymphocytes. It is believed that T-helper 2 (Th2) cells play a crucial role and cytokines secreted by them are very important for the pathogenesis of asthma. Corticosteroids are very effective on treating asthma, but long-term corticosteroid treatment causes serious side effects. Macrolide antibiotics have been shown to exhibit anti-inflammatory functions besides of its antibacterial effect. In several clinical trials of chronic pulmonary disease including asthma, the treatment with macrolide antibiotics show improved lung function and decrease cytokine or cell infiltration. Macrolide antibiotics have been also reported to inhibit cell proliferation, modulate proinflammatory and inflammatory cytokine secretion, and induce apoptosis of both unstimulated and stimulated lymphocytes. Azithromycin (AZM) is an advanced macrolide antibiotic. Because of activated T cells play a pivotal role in asthma, we examined weather AZM could suppress the functions of activated CD4+ T cells (Th0), Th1-biased cells (Th1), or Th2-biased cells (Th2). The effect of AZM on healthy or atopic donor cells was also evaluated. The data demonstrated that AZM inhibited IL-5 secretion (Th2 response) in a dose-dependent manner in atopic groups. However, AZM did not significantly inhibit IFN- expression (Th1 response) in asthmatic groups. Owing to Th1 and Th2 responses are counter-regulated, our finding suggests a therapeutic potential for using AZM in controlling asthma. Moreover, 50 ug/ml AZM inhibited cell proliferation and induced cell apoptosis. Although AZM did not significantly reduce cytokine levels per activated T cell, cytokine mRNA expressions were slightly decreased on AZM-treated cells. Thus, the inhibition of cell numbers and cytokine mRNA levels might explain the anti-inflammatory effects of AZM.