In COPD, inflammatory and structural cells also produce remodeling-associated cytokines. A few inflammatory mediators seem to play an important role in triggering the cascade of events leading to COPD. IL-8, TNF-a, TGF-, and leukotriene B4 are mostly reported in COPD inflammation. Understanding the exact implication of mediators and finding new pertinent mediators will help to improve our knowledge of COPD pathogenesis. Many of these cytokines have chemotactic properties to inflammatory cells, but little information is available on the mechanisms leading to irreversible bronchial structural alterations in COPD. Pathogenesis of COPD can be summarized as being an induced oxidative stress for epithelial cells and macrophages caused by cigarette smoke. read only
Then, the oxygen-free reactive radicals trigger an inflammatory pattern through che-mokine production by epithelial cells leading to neutrophil, CD8+ T-cell, eosinophil, and macrophage recruitment. The inflammatory process is believed to induce structural cell apoptosis and tissue degradation leading to chronic bronchitis and emphysema. Epithelial cells release other mediators (insulin-like growth factor-1, prostaglandin, fi-bronectin), thereby activating fibroblast recruitment and proliferation, matrix synthesis and, therefore, remodeling. In a murine model of emphysema, interferon-7 produced by CD8+ T-cells triggers COPD remodeling by modulation of protease and antiprotease synthesis. Proteases are produced by inflammatory cells as well as resident cells. The reported proteases and antiproteases implicated in COPD include neutrophil elastase, proteinase 3, cathepsins, MMP-1, MMP-9, MMP-2, a1-antitrypsin, secretory leukocyte proteinase inhibitor (SLPI), elafin, and TIMP. MMP-2 and MMP-9 are increased in COPD BAL fluid, with a greater increase being observed in the levels of MMP-9 as demonstrated by zymography studies.135 Furthermore, an increased level of MMP-1, MMP-2, MMP-9, and MMP-8 is found by immunocytochemistry in epithelial cells, fibroblasts, endothelial cells, macrophages, and neutrophils. MMP-9 and MMP-8 are mainly expressed by neutrophils, while MMP-1 and MMP-2 are restricted to macrophages and epithelial cells. All these various mechanisms associated with cigarette smoke may lead to lung remodeling in COPD.