Cigarette smoking decreases interleukin 1 release by human alveolar macrophages

G. P. Brown, G. K. Iwamoto, M. M. Monick and G. W. Hunninghake Department of Internal Medicine, Veterans Administration, Iowa City, Iowa 52242. To determine whether alveolar macrophages from smokers have an abnormal interleukin 1 beta (IL-1) release, we obtained macrophages by bronchoalveolar lavage (BAL) of otherwise healthy volunteers in three groups: nonsmokers (NS; n = 11), light smokers (LS, less than 10 pack-yr smoking history; n = 4) and heavy smokers (HS, greater than 10 pack-yr smoking history; n = 9). After 24 h in culture, unstimulated macrophages (from each group) released negligible amounts of IL-1. Lipopolysaccharide (LPS) (1 micrograms/ml) caused release of 21.77 +/- 4.33 ng IL-1/10(6) cells at 24 h from NS macrophages; IL-1 release from HS macrophages was significantly decreased (5.52 +/- 1.66 ng/10(6) cells; P less than 0.05), whereas LS macrophages released intermediate amounts (15.07 +/- 6.15 ng/10(6) cells). Release of IL-1 from HS macrophages was also decreased after 48 and 72 h in culture and was observed over a wide range of concentrations of LPS. The decreased amount of IL-1 in HS macrophage supernatants appeared to be due to a defect in release of IL-1 from the cells and not due to a defect in production of the mediator, since total IL-1 (IL-1 present in the cell lysates plus that in the cell supernatants) was similar in the NS and HS groups. In addition, after 24 h in culture, LPS-stimulated HS macrophages released significantly less prostaglandin E2 (PGE2) (which can suppress IL-1 production) than did NS macrophages; in the presence of indomethacin, which abolished macrophage PGE2 release, no augmentation of LPS-stimulated IL-1 release was observed. Cell viability, as measured by lactate dehydrogenase release, was not different between HS and NS macrophages under any conditions. We conclude that there is a defect in release but not production of IL-1 from the alveolar macrophages of chronic smokers.