Immunomodulatory effects of cigarette smoke
Introduction
Tobacco smoke is a complex mixture of thousands of different chemicals many of which have toxic and/or carcinogenic activity (Stedman, 1968; Hoffmann et al., 1979). The constituents of mainstream tobacco smoke (smoke drawn into the mouth during puffs) are principally encountered by smokers; environmental tobacco smoke (smoke originating mostly from the smoldering end of a cigarette between puffs and exhaled mainstream tobacco smoke) is responsible for involuntary or `passive' smoking by non-smokers (US Department of Health and Human Services, 1993).
Bioassays using tobacco smoke have shown that the majority of genotoxic and carcinogenic substances as well as nicotine are present in the particulate phase (material from cigarette smoke retained by the Cambridge filter comprised mostly of particles >0.1 μm diameter) of mainstream cigarette smoke (Dube and Green, 1982). The vapor phase (substances that pass through the Cambridge filter), has several known carcinogens, but has not been shown to be tumorigenic in inhalation assays (Hoffmann and Wynder, 1986).
Interest in understanding the mechanism of action by which cigarette smoke/nicotine influences the immune system stems from the recognition that tobacco smoking is a major cause of mortality and morbidity, responsible for over 400,000 deaths yr−1 in the United States; the direct health care costs related to cigarette smoking exceed US$50 billion yr−1 (US Department of Health and Human Services, 1994). Tobacco smoke has been demonstrated to significantly increase the incidence of heart disease, cancer at various sites, in particular the lung, and susceptibility to respiratory diseases (US Department of Health, Education and Welfare, 1979). Moreover, some recent data suggest that smoking may be a risk factor in faster development of AIDS in HIV-1-seropositive individuals, higher susceptibility of AIDS patients to develop Pneumocytis carinii infections, and higher frequency of transmission of AIDS from smoking mothers to their offspring (Burns et al., 1991; Nieman et al., 1993; Burns et al., 1994).
In recent years, there has been growing concern that non-smokers may also be at risk for some of the cigarette smoke-associated diseases as a result of involuntary exposure to environmental tobacco smoke. Despite quantitative differences, the chemical composition of environmental tobacco smoke is very similar to mainstream tobacco smoke and may predispose people to lung cancer and increased risks for lower respiratory tract infections (US Department of Health and Human Services, 1993).
Increased susceptibility of smokers to respiratory tract diseases and cancer may reflect cigarette smoke-induced impairment of the immune system (Holt and Keast, 1977). It has recently been postulated that atherosclerosis, which is significantly more prevalent in smokers, may also be an immunologically mediated disease (Wick et al., 1995). Thus, most of the deleterious effects of tobacco smoke on human health may reflect the adverse effects of tobacco smoke on the immune system. Immunosuppressive properties of cigarette smoke have been well established in a variety of experimental animal models and humans (Johnson et al., 1990; Sopori et al., 1994). However, the manner in which cigarette smoke affects the immune system is not clearly understood. There is increasing evidence that nicotine, a major component in cigarette smoke, may significantly contribute to cigarette smoke-induced immunosuppression (Sopori et al., 1993). This review will mainly focus on the effects of various components of cigarette smoke on the immune system and potential mechanisms through which cigarette smoke may affect the immune response.
Section snippets
Effects of cigarette smoke on the human immune system
The possibility that human diseases associated with cigarette smoke reflect the effects of tobacco smoke on the immune system was recognized in the 1960s (reviewed in Holt and Keast, 1977). Since then, a large body of evidence tends to support this inference (Holt, 1987; Johnson et al., 1990; Sopori et al., 1994). Human smokers are more likely to develop influenza and have lower antibody titers to influenza virus (Finklea et al., 1969; Aronson et al., 1982; Kark et al., 1982). Prenatal and
Effects of cigarette smoke on the immune system: animal studies
As in human studies, immunologic changes associated with cigarette smoke exposure are modified by several factors including the level and duration of exposure to cigarette smoke, tar and nicotine content of the smoke, and the species of the animal tested. Most of the animal studies have used rodents, especially rats and mice. There are inherent drawbacks in most rodent studies, because it is impractical to precisely replicate the characteristics patterns of human smoking. Thus, unlike humans,
Components of cigarette smoke that may affect the immune response
The observation that exposure to smoke from high-tar high-nicotine cigarettes is more immunosuppressive than the smoke from low-tar low-nicotine cigarettes (Holt et al., 1976), suggests that tar and nicotine may be important immunotoxic components within cigarette smoke. Most of the tar, nicotine, and genotoxicity of cigarette smoke is associated with the particulate phase of cigarette smoke (Hoffmann et al., 1979; Hoffmann and Wynder, 1986). Chronic exposure of rats to the vapor phase of
Mechanism(s) of cigarette smoke-induced changes in the immune system
From the above discussion, it is clear that chronic exposures to cigarette smoke suppress the antibody response, and nicotine may significantly contribute to this immunosuppression. Xenobiotics have been shown to affect immunoregulation by several mechanisms and cigarette smoke/nicotine could potentially affect the immune system by the following mechanisms.
Conclusion
Based on available scientific evidence, chronic exposure to mainstream and sidestream tobacco smoke appears to impair the immune system in man and experimental animals. In addition, both mainstream and sidestream tobacco smoke may cause airway hyperreactivity. Cigarette smoke is a complex mixture of thousands of different chemical compounds and, depending on the dose and time period of exposure, some of these may cause immunostimulation or immunosuppression (Sopori et al., 1994). Recent
Acknowledgements
This work was supported in part by grants from the National Institute of Drug Abuse DA04208 and DA05662. We thank Dr. M.I. Luster (National Institute for Occupational Safety and Health, Morgantown, WV) for his helpful suggestions about the manuscript.
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