Cigarette smoking decreases interleukin 1 release by human alveolar macrophages.
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.
Department of Internal Medicine, Veterans Administration, Iowa City, Iowa 52242.
G P
GP
Brown
G K
GK
Iwamoto
M M
MM
Monick
G W
GW
Hunninghake
D000328:Adult; D002478:Cells, Cultured; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D012907:Smoking / Q000503:physiopathology*
D007375:Interleukin-1; D008070:Lipopolysaccharides