The effect of cigarette smoke–derived oxidants on the inflammatory response of the lung

Abstract

The inhalation of cigarette smoke triggers a marked cellular influx in the lung, and this inflammation is believed to play a central role in the development of smoke-related lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). Studies demonstrate that smoke-derived oxidants are a major factor in this inflammatory reaction to cigarette smoke. These oxidants can overwhelm the lung's antioxidant defenses, and they can upregulate inflammation by a number of mechanisms. Free radicals directly stimulate the production of chemotactic compounds such as 8-isoprostane. In addition, smoke-derived oxidants can activate several intracellular signaling cascades including nuclear factor kappa B, mitogen-activated protein kinase, and AP-1. This transcriptional activation induces the expression of cytokines and intracellular adhesion molecules that facilitate the trafficking of neutrophils, macrophages, and lymphocytes into the lung. Moreover, oxidants can promote chromatin remodeling that facilitates the expression of proinflammatory genes by stimulating the acetylation of histone residues in the nucleosome. This leads to conformational changes that enhance expression by rendering the gene more accessible to binding to transcriptional factors. Thus, the oxidant–antioxidant imbalance generated by cigarette smoke can promote inflammation, which is critical to the functional decline that occurs in both asthma and COPD patients. Future research is needed to better define the effects of smoke-derived oxidants on lung inflammation and to determine the most efficacious strategies for generating significant antioxidant protection in the lung.