Thalidomide prevents cigarette smoke extract-induced lung damage in mice

• We described the inhibitory effects of thalidomide on pulmonary emphysema in mice.
• We showed the preventive and therapeutic effect of thalidomide.
• Thalidomide decreased the expression of IL-1β and IL-6 in lung epithelial cells.
• Thalidomide decreased apoptosis in the mouse lung.
• The results provide the clinical use of thalidomide for the treatment of emphysema.

Chronic obstructive pulmonary disease (COPD) is characterized by a progressive airway obstruction that is not completely reversible and is mainly caused by smoking tobacco. COPD is a major cause of morbidity and mortality worldwide and there are currently no proven effective treatments. The pathogenesis of COPD involves several factors such as chronic inflammation, oxidative stress, and apoptosis. Cytokines play important roles in chronic inflammation. Thalidomide (Thal) has been used to treat multiple myeloma due to its inhibitory effects on IL-6-induced cell growth. We recently demonstrated that thalidomide (Thal) played important roles in cytokine-induced lung damage in a bleomycin-induced pulmonary fibrosis model in mice. We herein examined the preventative effects of Thal on cigarette smoke extract (CSE)-induced emphysematous changes in mice.We performed histological examinations and quantitative measurements of the expression of IL-1β and IL-6 mRNA, as well as apoptosis in CSE-induced mouse lung tissues treated with or without Thal.The results of the histological examination showed that Thal ameliorated CSE-induced emphysema in mice. It also inhibited the expression of IL-1β and IL-6 mRNA in mouse lung tissues. Thal decreased apoptosis in the mouse lung. In vitro studies revealed that Thal decreased 1) the expression of IL-1β and IL-6 in human lung epithelial cells, and 2) CSE-induced apoptosis and the inhibition of cell growth, which may be the underlying mechanisms for the preventative effects of Thal on emphysema. These results provide a rationale for exploring the clinical use of Thal for COPD.