Tissue inhibitor of metalloproteinase-1 levels in bronchoalveolar lavage fluid from asthmatic subjects

Airway remodeling is a well-recognized feature in patients with chronic ast hma. The accumulation in the submucosa of fibrous proteins that are substra tes of matrix metalloproteinases (MMP), and the demonstration of increased levels of MMP-9 in bronchoalveolar lavage fluid, prompted us to determine w hether there was an imbalance between MMPs and tissue inhibitors of metallo proteinase (TIMP) in such patients. We investigated the presence of TIMPs a nd other MMPs. TIMP levels were compared with those of all MMPs and inflamm atory cytokines. Adults with stable asthma, either untreated or treated wit h glucocorticoids (GCs), were enrolled. Healthy nonsmokers served as a cont rol population. MMPs and TIMPs were identified through zymography or immuno blotting. TIMPs, MMPs, and cytokines were measured with enzyme immunoassays . TIMP-1 levels were significantly higher in untreated asthmatic subjects t han in CC-treated subjects or controls (p < 0.0001), and were far greater t han those of MMP-1, MMP-2, MMP-3, and MMP-9 combined. TIMP-2 was undetectab le. TIMP-1 levels were correlated with levels of interleukin-6 (p < 0.012) and the number of alveolar macrophages recovered (p < 0.005). This observat ion has important implications, since an excess of TIMP-1 could lead to air way fibrosis, a hallmark of airway remodelling in patients with chronic ast hma.