ALTERED CYTOKINE REGULATION IN THE LUNGS OF CIGARETTE SMOKERS

Cigarette smoking is the major factor responsible for chronic obstruct ive lung disease, but it occurs in only a minority of smokers. Smoking is associated with increased susceptibility to pulmonary infections a nd with a neutrophil- and macrophage-rich inflammation of the small ai rways. We compared concentrations of tumor necrosis factor (TNF), inte rleukin (IL)-6, and IL-8 in bronchoalveolar ravage fluid (BALF) and me asured the capacity of BALF macrophages to release TNF and IL-6 in vit ro in nine smokers (19.1 +/- 4.2 pack-years; mean +/- SE) and nine non smokers. Compared with nonsmokers, BALF from smokers contained more ce lls (65.3 +/- 13.2 versus 27.2 +/- 4.8 x 10(6); p < 0.02), but much lo wer 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 incr eased BALF concentrations of interleukin-8 (IL-8), but there was no di fference in BALF IL-8 concentrations between the two groups (p = 0.08) . Compared with BALF macrophages from nonsmokers, cells from smokers r eleased less TNF (211 +/- 77 versus 1,406 +/- 348 units per 10(6) cell s; p < 0.01) and IL-6 (5.8 +/- 2.6 versus 64.9 +/- 23.3 hybridoma unit s per ml; p < 0.02) during a 6-h incubation with lipopolysaccharide (L PS). We conclude that even in young, healthy smokers the pulmonary mic roenvironment is markedly abnormal, characterized by depressed levels of IL-6, macrophages that have a markedly depressed capacity for LPS-i nduced cytokine release and, in some smokers, increased concentrations of IL-8.