Y Ouyang1, N Virasch, P Hao, M T Aubrey, N Mukerjee, B E Bierer, B M Freed. 1. Clinical Immunology and Histocompatibility Laboratory, Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Health Sciences Center, Denver, USA.
Abstract
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. CONCLUSION: These studies indicate that cigarette smoke contains potent inhibitors of cytokine production, at least one of which is present even in low-tar cigarettes.
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. CONCLUSION: These studies indicate that cigarette smoke contains potent inhibitors of cytokine production, at least one of which is present even in low-tar cigarettes.
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