Cigarette smoking decreases bioactive interleukin-6 secretion by alveolar macrophages.
Studies suggest smokers have decreased alveolar macrophage (AM) accessory cell (AC) function and a reduced incidence of immune-mediated lung diseases such as sarcoidosis. Impaired AM secretion of cytokines important in T-cell immune responses could explain this observation. We investigated production and secretion of interleukin-1 (IL-1) and interleukin-6 (IL-6) in smokers and nonsmokers. Lipopolysaccharide-induced AM IL-1 secretion in smokers was significantly reduced compared with nonsmoker AM. However, intracellular IL-1 in smoker AM was higher than in nonsmokers, suggesting that reduced IL-1 secretion was due to impaired release rather than reduced production. Smoker AM secreted significantly less bioactive IL-6 measured in a bioassay compared with nonsmoker AM. Intracellular IL-6 was virtually undetectable in both groups. In some smokers IL-6 production determined by immunoprecipitation was reduced. However, as a group antigenic IL-6 secretion determined by enzyme-linked immunoabsorbent assay was similar in smokers and nonsmokers, suggesting that smoker AM may cosecrete an inhibitor of IL-6 bioactivity. Indeed, AM supernatants from smokers inhibited B9 proliferation in response to maximal recombinant IL-6 stimulation, whereas supernatants from nonsmokers did not. We conclude that AM from smokers secrete less cytokines important in T-cell proliferation than AM from nonsmokers and suggest that for IL-6 this impairment is related to both decreased production of antigenic protein as well as cosecretion of an IL-6 inhibitor.
Soliman
D M
DM
Department of Medicine, Indiana University Medical Center, Indianapolis 46202.
Twigg
H L
HL
D000328:Adult; D000941:Antigens / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D012907:Smoking; D000093242:Interleukin-6 Inhibitors
D000941:Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000093242:Interleukin-6 Inhibitors