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 10(6); 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 10(8) 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.
McCrea
K A
KA
Department of Medicine, University of Maryland School of Medicine, Baltimore.
Ensor
J E
JE
Nall
K
K
Bleecker
E R
ER
Hasday
J D
JD
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008168:Lung / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D012907:Smoking / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha