Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers - Regulation by interleukin-10

An imbalance between proteases and antiproteases may play a role in emphyse ma, which is characterized by increased degradation of extracellular matrix , and in airway remodeling in chronic bronchitis and asthma, in which there is increased collagen deposition. We assessed the effect of smoking on rel ease of matrix metalloprotease-9 (MMP-9) and of its inhibitor, tissue inhib itor of metalloprotease-1 (TIMP-1), from alveolar macrophages, and determin ed the effects of proinflammatory (interleukin [IL]-1 beta and lipopolysacc haride [LPS]) and antiinflammatory (IL-10) stimuli on the release of MMP-9 and TIMP-1. We performed bronchoalveolar lavage in 11 smokers and 11 nonsmo kers, and cultured airway macrophages in the presence of control medium, IL -1 beta, and LPS. Airway macrophages from smokers released greater amounts of MMP-9 and TIMP-1 at baseline and in response to IL-1 beta and LPS than d id those of nonsmokers. Airway macrophages from smokers produced more TNF-a lpha and IL-10. IL-10 increased TIMP-1 release without modifying that of MM P-9, leading to a decrease in the MMP-9 to TIMP-1 ratio. Anti-IL-10 antibod y had no effect on MMP-9 production induced by LPS. We conclude that the re lease of proteases and antiproteases by airway macrophages is increased in cigarette smokers, and can be regulated by exogenous IL-10.