Altered cytokine regulation in the lungs of cigarette smokers

Cigarette smoking is the major factor responsible for chronic obstructive lung disease, but it occurs in only a minority of smokers. Smoking is associated with increased susceptibility to pulmonary infections and with a neutrophil- and macrophage-rich inflammation of the small airways. We compared concentrations of tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 in bronchoalveolar lavage fluid (BALF) and measured the capacity of BALF macrophages to release TNF and IL-6 in vitro in nine smokers (19.1 ± 4.2 pack-years; mean ± SE) and nine nonsmokers. Compared with nonsmokers, BALF from smokers contained more cells (65.3 ± 13.2 versus 27.2 ± 4.8 x 10⁶; p < 0.02), but much lower concentrations of IL-6 (1.8 ± 1.0 versus 15.9 ± 5.8 pg/ml; p < 0.05). The two smokers with the highest number of BALF cells had increased BALF concentrations of interleukin-8 (IL-8), but there was no difference in BALF IL-8 concentrations between the two groups (p = 0.08). Compared with BALF macrophages from nonsmokers, cells from smokers released less TNF (211 ± 77 versus 1,406 ± 348 units per 10⁶ cells; p < 0.01) and IL-6 (5.8 ± 2.6 versus 64.9 ± 23.3 hybridoma units per ml; p < 0.02) during a 6-h incubation with lipopolysaccharide (LPS). We conclude that even in young, healthy smokers the pulmonary microenvironment is markedly abnormal, characterized by depressed levels of IL-6, macrophages that have a markedly depressed capacity for LPS-induced cytokine release and, in some smokers, increased concentrations of IL-8.