Suppression of human IL-1beta, IL-2, IFN-gamma, and TNF-alpha production by cigarette smoke extracts.
BACKGROUND
Although cigarette smoking is known to have detrimental effects on the immune system, the nature of the immunosuppressive agent or agents is poorly understood.


OBJECTIVE
The purpose of the current study was to evaluate the effects of cigarette smoke extracts from high-tar (unfiltered Camel), medium-tar (Marlboro), and low-tar (Carlton) cigarettes on the in vitro production of IL-1beta, IL-2, IFN-gamma, and TNF-alpha.


METHODS
The concentrations of hydroquinone and catechol in cigarette smoke extracts were determined by using HPLC. Human PBMCs were treated with cigarette smoke extracts, hydroquinone, or catechol, and stimulated with anti-CD3 and phorbol-12-myristate-13-acetate. Cytokine levels in the supernatants were quantified by ELISA.


RESULTS
Pretreatment of PBMCs with cigarette smoke extracts derived from a single high- or low-tar cigarette suppressed the production of IL-1beta, IL-2, IFN-gamma, and TNF-alpha by greater than 90% without significant loss of cell viability. Nicotine, at a concentration comparable with that found in the highest-tar cigarettes (200 microg/mL), suppressed the production of IL-2, IFN-gamma, and TNF-alpha by only 21% to 38%. Catechol (50 micromol/L) inhibited production of IL-2 and IL-1beta by 62% to 73% but had little effect on TNF-alpha or IFN-gamma production. In contrast, hydroquinone inhibited the production of all 4 cytokines with IC(50) values ranging from 3 micromol/L(IL-1beta) to 29 micromol/L (IFN-gamma). However, HPLC determination of the hydroquinone concentrations in cigarette smoke extracts from single Camel (33+/-4 micromol/L), Marlboro (13+/-2 micromol/L), and Carlton (<1 micromol/L) cigarettes clearly demonstrated that the potent inhibitory effects of the low-tar cigarettes could not be accounted for by either hydroquinone or catechol.


CONCLUSIONS
These studies indicate that cigarette smoke contains potent inhibitors of cytokine production, at least one of which is present even in low-tar cigarettes.
Ouyang
Y
Y
Clinical Immunology and Histocompatibility Laboratory, Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Health Sciences Center, Denver, USA.
Virasch
N
N
Hao
P
P
Aubrey
M T
MT
Mukerjee
N
N
Bierer
B E
BE
Freed
B M
BM
D000975:Antioxidants / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D009538:Nicotine / Q000494:pharmacology; D010947:Plants, Toxic; D012906:Smoke; D014026:Nicotiana; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000975:Antioxidants; D002396:Catechols; D005731:Ganglionic Stimulants; D006873:Hydroquinones; D007375:Interleukin-1; D007376:Interleukin-2; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; D009538:Nicotine; D007371:Interferon-gamma; C034221:catechol; C031927:hydroquinone