Cytostatic activity of alveolar macrophages from smokers and nonsmokers: role of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha.
Several functions of alveolar macrophages (AM) are modified by cigarette smoking. AM are the first line of defense in bronchoalveolar spaces and could be depressed in their cytotoxicity to tumor cells in smokers. An assay using A549 cells (human lung adenocarcinoma) as target cells was performed to assess cytostasis mediated by AM and their supernatants (SN) from healthy smokers (n = 8) and nonsmokers (n = 6). Contact-mediated cytostasis was decreased in AM of smokers (n = 8) relative to nonsmokers (n = 6) (22.9 +/- 5.7% versus 42.7 +/- 6.0% [+/- SEM], P < 0.04) and increased after lipopolysaccharide (LPS) stimulation in both groups (34.5 +/- 5.3% versus 46.8 +/- 5.2%, NS). Cytostasis induced by SN from nonstimulated AM was low in both groups and was still lower in smokers after LPS exposure (19.3 +/- 4.5% versus 34.5 +/- 4.8%, P < 0.04). Among cytotoxic factors produced by macrophages, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) may play an important role in cytostasis. Recombinant human (rH) IL-1 beta and rHTNF alpha had a moderate cytostatic activity, which was additive, whereas rHIL-6 had no significant activity on A549 cells. Bioactive IL-1 beta, IL-6, and TNF alpha were therefore measured in macrophage SN. Their levels tended to be lower in smokers than in nonsmokers and were much increased after LPS stimulation. Levels of the three cytokines were also found to correlate with each other; furthermore, a good correlation between cytokine levels in SN and cytostasis was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Sauty
A
A
Department of Internal Medicine, University Hospital, University of Lausanne, Switzerland.
Mauel
J
J
Philippeaux
M M
MM
Leuenberger
P
P
D000230:Adenocarcinoma / Q000276:immunology; D000328:Adult; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D012907:Smoking / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha