Mechanisms of allergy
Suppression of human IL-1β, IL-2, IFN-γ, and TNF-α production by cigarette smoke extracts,☆☆,

https://doi.org/10.1067/mai.2000.107751Get rights and content

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-1β, IL-2, IFN-γ, and TNF-α. 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-1β, IL-2, IFN-γ, and TNF-α by greater than 90% without significant loss of cell viability. Nicotine, at a concentration comparable with that found in the highest-tar cigarettes (200 μg/mL), suppressed the production of IL-2, IFN-γ, and TNF-α by only 21% to 38%. Catechol (50 μmol/L) inhibited production of IL-2 and IL-1β by 62% to 73% but had little effect on TNF-α or IFN-γ production. In contrast, hydroquinone inhibited the production of all 4 cytokines with IC50 values ranging from 3 μmol/L(IL-1β) to 29 μmol/L (IFN-γ). However, HPLC determination of the hydroquinone concentrations in cigarette smoke extracts from single Camel (33 ± 4 μmol/L), Marlboro (13 ± 2 μmol/L), and Carlton (<1 μmol/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. (J Allergy Clin Immunol 2000;106:280-7.)

Section snippets

Preparation of cigarette smoke extracts, hydroquinone, catechol, and nicotine solutions

Cigarette smoke extracts were freshly prepared by bubbling smoke drawn from single lit commercial cigarettes representing high-tar (unfiltered Camel; R. J. Reynolds Tobacco Co, Winston-Salem, NC; 26 mg of tar and 1.7 mg of nicotine per cigarette), medium-tar (Marlboro; Philip Morris Inc, Richmond, Va; 15 mg of tar and 0.9 mg of nicotine per cigarette), and low-tar cigarettes (Carlton 100's; Brown & Williamson Tobacco Corp, Louisville, Ky; 1 mg of tar and 0.1 mg of nicotine per cigarette)

HPLC analysis of cigarette smoke extracts

Cigarette smoke extracts of Camel (unfiltered), Marlboro, and Carlton cigarettes were analyzed by C18 reverse-phase HPLC and monitored by tandem UV and electrochemical detectors (Fig 1).

. Chromatographic profiles of Camel, Marlboro, and Carlton smoke extracts. The chromatographic profiles of Camel (A) , Marlboro (B) , and Carlton (C) extracts were determined by using reverse-phase HPLC monitored with a UV detector at 280 nm and an electrochemical detector at 0.7 V (inset) . The results are

Discussion

The proinflammatory cytokines IL-1β, TNF-α, IL-2, and IFN-γ play important roles in the host defense against infection and cancer.24, 25, 26, 27 All 4 cytokines are involved in the generation of lymphokine-activated killer cells and cytotoxic T cells that are capable of destroying lung tumors.28, 29, 30, 31, 32, 33 Several studies have shown that progressive tumor growth is associated with decreased antitumor immunity and lower levels of IL-2 and IFN-γ.34, 35, 36 Decreased serum IL-1, IL-2, and

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    Dr Bierer is currently affiliated with the Laboratory of Lymphocyte Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Md.

    ☆☆

    Supported by National Institutes of Health grants ES05673 and HL60538.

    Reprint requests: Brian M. Freed, PhD, Clinical Immunology and Histocompatibility Laboratory, Division of Allergy and Clinical Immunology, University of Colorado Health Sciences Center, Campus Box B164, 4200 E Ninth Ave, Denver, CO 80262.

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