Acrolein in cigarette smoke inhibits T-cell responses.
BACKGROUND
Cigarette smoking inhibits T-cell responses in the lungs, but the immunosuppressive compounds have not been fully identified. Cigarette smoke extracts inhibit IL-2, IFN-gamma, and TNF-alpha production in stimulated lymphocytes obtained from peripheral blood, even when the extracts were diluted 100-fold to 1000-fold.


OBJECTIVE
The objective of these studies was to identify the immunosuppressive compounds found in cigarette smoke.


METHODS
Gas chromatography/mass spectroscopy and HPLC were used to identify and quantitate volatile compounds found in cigarette smoke extracts. Bioactivity was measured by viability and production of cytokine mRNA and protein levels in treated human lymphocytes.


RESULTS
The vapor phase of the cigarette smoke extract inhibited cytokine production, indicating that the immunosuppressive compounds were volatile. Among the volatile compounds identified in cigarette smoke extracts, only the alpha,beta-unsaturated aldehydes, acrolein (inhibitory concentration of 50% [IC50] = 3 micromol/L) and crotonaldehyde (IC50 = 6 micromol/L), exhibited significant inhibition of cytokine production. Although the levels of aldehydes varied 10-fold between high-tar (Camel) and ultralow-tar (Carlton) extracts, even ultralow-tar cigarettes produced sufficient levels of acrolein (34 micromol/L) to suppress cytokine production by >95%. We determined that the cigarette smoke extract inhibited transcription of cytokine genes. The inhibitory effects of acrolein could be blocked with the thiol compound N-acetylcysteine.


CONCLUSIONS
The vapor phase from cigarette smoke extracts potently suppresses cytokine production. The compound responsible for this inhibition appears to be acrolein.
Lambert
Cherie
C
Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA.
McCue
Jesica
J
Portas
Mary
M
Ouyang
Yanli
Y
Li
JiMei
J
Rosano
Thomas G
TG
Lazis
Alexander
A
Freed
Brian M
BM
D000111:Acetylcysteine / Q000494:pharmacology; D000171:Acrolein / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000633:toxicity*; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000633:toxicity; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012906:Smoke / Q000009:adverse effects* / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D014026:Nicotiana / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D012333:RNA, Messenger; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; D000171:Acrolein; D007371:Interferon-gamma; D000111:Acetylcysteine