Inflammatory response of lung macrophages and epithelial cells to tobacco smoke: A literature review of ex vivo investigations

Chronic inflammation contributes to the initiation and progression of tumors and tobacco smoke-associated inflammation is associated with malignant and certain non-neoplastic lung diseases. Reported herein are the results of an interpretative synthesis review of the literature assessing the inflammatory response of lung macrophages (MΦ) and epithelial cells to tobacco smoke as measured ex vivo. Papers were retrieved using Boolean operations from PubMed and Scopus. Many writings reported the results of assays of human MΦ from fresh surgically excised human lung tissue, bronchoalveolar lavage, activated blood monocytes, long-term cell lines and MΦ from different laboratory animals. Some publications reported the findings of comparative studies of lung MΦ freshly isolated from the lungs of smokers and non-smokers. Other papers described the effect of tobacco smoke on lung epithelial cells. Most investigators quantified the response of the target cells to tobacco smoke by measuring the production of pro-inflammatory mediators; these included chemokines, cytokines, reactive oxygen species and enzymes. Investigators have reported conflicting observations of the response of human and animal MΦ and epithelial cells to tobacco smoke. The spectrum included papers describing robust production of various inflammatory mediators, significant reduction of a pro-inflammatory response to a known stimulant and overt cytotoxicity. This literature review documents that there exists no consensus, and no emerging trend line, of the reproducible effect(s) of cigarette smoke. This discrepancy reflects the absence of standardized protocols for collecting, processing and bioassaying the smoke, a highly complex aerosol, and identifies the need for establishing collaborative research schemes.