The exposure to cigarette
smoke (CS) is associated with
emphysema. In addition to chronic
lung inflammation,
emphysema is known mainly for the complex pathogenesis associated with imbalance of proteolytic and antiproteolytic activities, oxidative stress, and apoptosis of lung structural cells. Increasing evidence shows that
erythromycin, which is a
macrolide antibiotic, ameliorates chronic
inflammation via mechanisms independent of its antibacterial activity. We hypothesize that
erythromycin protects against CS-induced
emphysema and
inflammation in rats via its anti-
inflammation and antiapoptosis action. Sprague-Dawley (SD) rats were administered
lipopolysaccharide (LPS) intratracheally
solution twice and exposed to the CS, the control rats were administered saline intratracheally and exposed to ambient air for 3 weeks. Then, all the CS rats were distributed randomly into 3 groups and, respectively, treated orally with saline (LPS + CS + saline), Guilongkechuanning
capsule (450 mg/kg) (LPS + CS + GLKCN), or
erythromycin (100 mg/kg) (LPS + CS + ERY) 0.5 h before CS exposure for 2 weeks. On day 36, the rats were killed. The
cytokines in serum were measured by
enzyme-linked
immunosorbent assay (ELISA). The middle lobe of the right lung was removed for histology and apoptosis analyses, respectively. Emphysematous lesions and inflammatory cell infiltrations in the CS group were evident by a histologic analysis.
Erythromycin protected significantly against the alveolar enlargement levels (P = 0.0017), reduced the pathologic apoptosis (P = 0.0023) related with Bcl-2 (P = 0.0002) and Bax (P = 0.0002), and inhibited the expressions of
matrix metalloproteinase (MMP)-9 (P = 0.0019) and
TIMP-1 protein (P = 0.04) and the
MMP-9/TIMP-1 ratio (P = 0.0002) in the lungs of CS-induced
emphysema in rats. The protective effect of
erythromycin on CS-induced
emphysema and
inflammation in rats is associated with a reduction in
inflammation, imbalance of
MMP-9/TIMP-1, and apoptosis of lung structural cells. However,
erythromycin did not recover completely the emphysematous morphologic changes to the levels when compared with control rats. This distinctive pattern implies that
erythromycin might have the potential to suppress airway
inflammation and maintain the integrity of airway epithelium to some extent.