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Acute effects of smoking and high experimental exposure to environmental tobacco smoke (ETS) on the immune system

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Abstract

Controversial results have been published on the immune response to cigarette smoking while the effects of exposure to environmental tobacco smoke (ETS) have not yet been reported. In a controlled study, acute effects of smoking and of a high environmental exposure to ETS on immunological parameters have been investigated. The study consisted of four experimental days, two control and two exposure days. On control days, 1 and 3, smokers (n=5) and nonsmokers (n=5) sat in an unventilated 45 m3 room for 8 h. On the exposure days, 2 and 4, each of the smokers smoked 24 cigarettes in 8 h, while the nonsmokers were exposed to the ETS generated by the smoking volunteers. Blood was drawn before and after each exposure session on all four experimental days for dosimetry of tobacco smoke exposure and determination of the immune response. Flow cytometry using monoclonal antibodies was used to determine CD3+ cells (whole T cells), CD19+ cells (B lymphocytes), CD16+ and CD56+ cells (natural killer cells), CD4+ cells (T-helper cells), CD8+ cells (T-suppressor cells), the CD4+/CD8+ (helper/supressor ratio), and Fc receptors on granulocytes. Serum was analyzed for soluble CD14 receptors (scD14), interleukin 1, interleukin 6 and prostaglandin E2 (PGE2). Functional stimulation assays were performed to determine the basal and induced level of reactive oxygen intermediate (ROI) production by polymorphic neutrophils. Exposure to tobacco smoke in both groups was confirmed by dosimetry of carboxyhemoglobin, plasma nicotine, and cotinine levels. In comparison to nonsmokers, smokers had elevated granulocyte cell counts, increased CD16+ and CD56+ cell levels and decreased CD3+ and CD19+ levels. Acute smoking, but not exposure to ETS, resulted in a slight decrease in the number of CD19+ cells and an increase in the number of granulocytes; the latter was restricted to one subject. Acute smoking and exposure to high experimental concentrations of ETS resulted in a slight increase in CD16+ and CD56+ cells. None of the changes determined in immunological parameters after either acute smoking or exposure to ETS reached statistical significance. Serum sCD14, cytokine and PGE2, functional stimulation of in vitro ROI production, and changes in Fc receptors were not affected by acute smoking or exposure to ETS. Although no clear guidelines exist to assess immunotoxicity in man, our data do not favor immunosuppression and the possibility of increased risk of infection in nonsmokers exposed to ETS under real-life conditions.

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Abbreviations

AM:

alveolar macrophage

BALF:

bronchoalveolar lavage fluid

CO:

carbon monoxide

CO2 :

carbon dioxide

COHb:

carboxyhemoglobin

ELISA:

enzyme linked immunoassay

ETS:

environmental tobacco smoke

FITC:

fluorescein isothiocyanate

IL:

interleukin

MHC:

major histocompatibility complex

NK:

natural killer cell

NO:

nitrogen oxide

NO2 :

nitrogen dioxide

PBS:

phosphate-buffered saline

PE:

phycoerythrin

PGE2 :

prostaglandin E2

PMA:

phorbol-12-myristate-13-acetate

PMN:

polymorphic neutrophils

RIA:

radioimmunoassay

ROI:

reactive oxygen intermediates

RSP:

respirable suspended particles

sCD14:

soluble CD14 receptor

References

  • Ada GL. Host factors important in immune surveillance against tumors. In: Bartsch H, Armstrong B, Davis W, eds. Host factors in human carcinogenesis. Lyon: International Agency for Research on Cancer; 1982; 223–39. (IARC Scientific Publication no. 39).

    Google Scholar 

  • Ancochea J, González A, Sánchez MJ, Aspa J, López-Botet M. Expression of lymphocyte activation surface antigens in bronchoalveolar lavage and peripheral blood cells from young healthy subjects. Chest. 1993;104:32–7.

    Google Scholar 

  • Bahne SL, Heiner DC, Myhre BA Changes in serum IgD in cigarette smokers. Clin Exp Immunol. 1983;51:624–30.

    Google Scholar 

  • Brown GP, Iwamoto GK, Monick MM, Gunninghake GW. Cigarette smoking decreases interleukin-1 release by human alveolar macrophages. Am J Physiol. 1989;256(Cell Physiol 25):C260–4.

    Google Scholar 

  • Conner JM, Oldaker G, Murphy JJ. Method for assessing the contribution of environmental tobacco smoke to respirable suspended particulate in indoor air. Environ Technol Lett. 1990;11:189–96.

    Google Scholar 

  • Dubois CM, Bissonnette E, Rola-Pleszczynski M. Asbestos fibre and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Am Rev Respir Dis. 1989;139:1257–64.

    Google Scholar 

  • Elias JA, Trinchieri G, Beck JM et al. A synergistic interaction of IL-6 and IL-1 mediates the thymocyte-stimulating activity produced by recombinant IL-1-stimulated fibroblasts. J Immunol. 1989;142:509–14.

    Google Scholar 

  • Emmendörffer A, Hecht M, Lohmann-Matthes ML, Roesler J. A fast and easy method to determine the production of reactive oxygen intermediates by human and murine phagocytes using dihydrorhodamine 123. J Immunol Methods. 1990;131: 269–75.

    Google Scholar 

  • Ferson M, Edwards AE, Lind A, Milton GW, Hersey P. Low natural killer-cell activity and immunoglobulin level associated with smoking in human subjects. Int J Cancer. 1979;23:603–9.

    Google Scholar 

  • Feyerabend C, Russell MAH. A rapid gas-liquid chromatographic method for the determination of cotinine and nicotine in biological fluids. J Pharm Pharmacol. 1990;42:450–2.

    Google Scholar 

  • Friedmam GD, Seigelaub AB, Seltzer CC, Feldman R, Collen MF. Smoking habits and the leukocyte count. Arch Environ Health. 1973;26:137–43.

    Google Scholar 

  • Galandrini R, Cernetti C, Albi N et al. Interleukin-6 is constitutively produced by human CTL clones and is required to maintain their cytolytic function. Cell Immunol. 1991;138:11–23.

    Google Scholar 

  • Gerrard JW, Heiner DC, Ko CG, Mink J, Meyers A, Dosman JA. Immunoglobulin levels in smokers and nonsmokers. Ann Allergy. 1980;44:261–2.

    Google Scholar 

  • Ginns LC, Goldenheim PD, Miller LG et al. T-lymphocyte subsets in smoking and lung cancer. Am Rev Respir Dis. 1982;126:265–9.

    Google Scholar 

  • Ginns LC, Ryu JH, Rogol PR, Sprince NL, Oliver LC, Larsson CJ. Natural killer cell activity in cigarette smokers and asbestos workers. Am Rev Respir Dis. 1985;131:831–4.

    Google Scholar 

  • Gmelig-Meyling F, Waldmann TA. One step separation of human blood monocytes and lymphocytes on Percoll gradient. J Immunol Methods. 1980;33:1–9.

    Google Scholar 

  • Hersey P, Prendergast D, Edwards A. Effects of cigarette smoking on the immune system. Follow-up studies in normal subjects after cessation of smoking. Med J Aust. 1983;2:425–9

    Google Scholar 

  • Hirano T, Taga T, Nakano N et al. Purification of homegeneity and characterization of human B cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci USA. 1985;82: 5490–4.

    Google Scholar 

  • Holsti MA, Raulet DH. IL-6 and IL-1 synergize to stimulate IL-2 production and proliferation of peripheral T cells. J Immunol. 1989;143:2514–9.

    Google Scholar 

  • Holt PG, Keast D. Environmentally induced changes in immunological function: Acute and chronic effects of inhalation of tobacco smoke and other atmospheric contaminants in man and experimental animals. Bacteriol Rev. 1977;41:205–16.

    Google Scholar 

  • Hughes DA, Haslam PL, Townsend PJ, Turner-Warwick M. Numerical and functional alterations in circulatory lymphocytes in cigarette smokers. Clin Exp Immunol. 1985;61:459–66.

    Google Scholar 

  • Irwin M, Patterson T, Smith TL et al. Reduction of immune function in life stress and depression. Biol Psychiatry. 1990;27:22–30.

    Google Scholar 

  • Jarvis MJ. Application of biochemical intake markers to passive smoking measurement and risk estimation. Mutat Res. 1989;222:101–10.

    Google Scholar 

  • Jezewska E, Dworacki G, Skrzypezak A, Zeromski J. Surface antigens and cytotoxic killer cell (NK) activity of blood lymphocytes in heavy cigarette smokers. Arch Geschwulstforsch. 1990;60:187–92.

    Google Scholar 

  • Johnson JD, Houchens DP, Kluwe WM, Craig DK, Fisher GL. Effect of mainstream and sidestream tobacco smoke on the immune system in animals and humans: A review. Toxicology. 1990;20:364–95.

    Google Scholar 

  • Knudsen PJ, Dinarello CA, Strom TB. Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate. J Immunol. 1986;137:3189–94.

    Google Scholar 

  • Landmann R, Fischer AE, Obrecht JP. Interferon-gamma and interleukin-4 down-regulate soluble CD14 release in human monocytes and macrophages. J Leukocyte Chem. 1992;52:323–30.

    Google Scholar 

  • Langone J, Gjika HB, Van Vunakis H. Nicotine and its metabolites: radioimmunoassay for nicotine and cotinine. Biochemistry. 1973;12:5025–30.

    Google Scholar 

  • Laughter AH, Martin RR, Twomey JJ. Lymphoproliferative responses to antigens mediated by human pulmonary alveolar macrophages. J Lab Clin Med. 1977;89:1326–32.

    Google Scholar 

  • Lauener RP, Geha RS, Vercelli D. Engagement of the monocyte surface antigen CD14 induces lymphocyte function-associated antigen-1/intercellular adhesion molecule-1-dependent homotypic adhesion. J Immunol. 1990;145:1390–4.

    Google Scholar 

  • Letzel HW, Johnson LC. The extent of passive smoking in the Federal Republic of Germany. Prev Med. 1984;13:717–29.

    Google Scholar 

  • Lotz M, Jirik F, Kabouridis P et al. B cell stimulation factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med. 1988;167:1253–8.

    Google Scholar 

  • Miller LG, Goldstein G, Murphy M, Ginns LC. Reversible alterations in immunoregulatory T-cells in smoking. Analysis by monoclonal antibodies and flow cytometry. Chest. 1982;82:526–9.

    Google Scholar 

  • Nagai S, Takeuchi M, Watanabe K, Aung H, Izumi T. Smoking and interleukin-1 activity released from human alveolar macrophages in healthy subjects. Chest. 1988;94:694–700.

    Google Scholar 

  • Neher GH. Nicotine-induced depression of lymphocyte growth. Toxicol Appl Pharmacol. 1974;27:253–8.

    Google Scholar 

  • Ogden MW. Gaschromatographic determination of nicotine in environmental tobacco smoke: Collaborative study. J Assoc Off Anal Chem. 1989;72:1002–6.

    Google Scholar 

  • Ogden MW, Maiolo K. Comparison of GC and LC for determining solanesol in environmental tobacco smoke. LC/GC. 1990;10:459–62.

    Google Scholar 

  • Phillips B, Marshall ME, Brown S, Thompson JS. Effects of smoking on human natural killer cell activity. Cancer. 1985;56:2789–92.

    Google Scholar 

  • Ritchie AWS, Gray RA, Micklem HS. Right angle light scatter: a necessary parameter in flow cytometric analysis of human peripheral blood mononuclear cells. J Immunol Methods. 1983;64:109–14.

    Google Scholar 

  • Schindler R, Mancilla J, Endres S, Ghorbani R, Clark SC, Dinarello CA. Correlations and interactions in the production of interleukin-6 (IL-6), IL-1 and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood. 1990;75:40–7.

    Google Scholar 

  • Schuett C, Schumann R. Der Endotoxinrezeptor CD14. Immunitat und Infektion. 1993;21:36–40.

    Google Scholar 

  • Schuett C, Ringel B, Nausch M, et al. Human monocyte activation induced by an anti-CD-14 monoclonal antibody. Immunol Lett. 1988;19:321–7.

    Google Scholar 

  • Soliman DM, Twigg HL. Cigarette smoking decreases bioactive interleukin-6 secretion by alveolar macrophages. Am J Physiol. 1992;263 (Lung Cell Mol Physiol 7):L471–8.

    Google Scholar 

  • Szadkowski D, Harke HP, Angerer J. Kohlenmonoxydbelastung durch Passivrauchen in Büroräumen. Inn Med. 1976;3:310–3.

    Google Scholar 

  • Takeuchi M, Nagai S, Izumi T. Effect of smoking on natural killer cell activity in the lung. Chest. 1988;94:688–93.

    Google Scholar 

  • Tollerud DJ, Clark JW, Brown LM et al. The effects of cigarette smoking on T cell subsets. A population-based survey of healthy caucasians. Am Rev Respir Dis. 1989a;139:1446–51.

    Google Scholar 

  • Tollerud DJ, Clark JW, Brown LM et al. Association of cigarette smoking with decreased numbers of circulating natural killer cells. Am Rev Respir Dis. 1989b;139:194–8.

    Google Scholar 

  • Tollerud DJ, Brown LM, Blatner, WA, Mann DL, Pankiwtrost LK, Hoover RN. T cell subsets in healthy black smokers and nonsmokers. Evidence for ethnic group as an important response modifier. Am Rev Respir Dis. 1991;144:612–6.

    Google Scholar 

  • Tomassen MJ, Barna BP, Wiedemann HP, Farmer M, Ahmad M. Human alveolar macrophage function: Differences between smokers and nonsmokers. J Leukocyte Biol. 1988;44:313–8.

    Google Scholar 

  • Tosato G, Jones KD. Interleukin-1 induces interleukin-6 in peripheral blood monocytes. Blood. 1990;75:1305–10.

    Google Scholar 

  • Tosato G, Seamon KB, Goldman NS et al. Identification of a monocyte-derived human B cell growth factor as interferon-2 (BSF-2; IL-6). Science. 1988;239:502–4.

    Google Scholar 

  • Trizio D, Basketter DA, Botham PA et al. Identification of immunotoxic effects of chemicals and assessment of their relevance in man. Fd Chem Toxicol. 1988;26:527–39.

    Google Scholar 

  • Turner S, Cyr L, Gross AR. The measurement of environmental tobacco smoke in 585 office environments. Environ Int. 1992;18:19–28.

    Google Scholar 

  • Von Poppel G, Spanhaak S, Ockhuizen T. Effect of β-carotene on immunological indexes in healthy male smokers. Am J Clin Nutr. 1992;57:402–7.

    Google Scholar 

  • Warren CPW, Holford-Stevens V, Wong C, Manfreda J. The relationship between smoking and total immunoglobulin E levels. J Allergy Clin Immunol. 1982;69:370–5.

    Google Scholar 

  • Wieslander E, Linden M, Hakansson L et al. Human alveolar macrophages from smokers have an impaired capacity to secrete LTB4 but not other chemotactic factors. Eur J Respir Dis. 1987;71:263–72.

    Google Scholar 

  • Windle M, Mondul T, Whitney RB, Cummings KM, Stadler I, Chadha KC. A discriminant function analysis of various interferon parameters among alcoholics and heavy smokers. Drug Alcohol Depend. 1993;31:139–47.

    Google Scholar 

  • Wolfe WH, Miner JC, Michalek JE. Immunological parameters in current and former US Air Force personnel. Vaccine. 1993;11:545–7.

    Google Scholar 

  • Yamaguchi E, Okazaki N, Itoh A, Abe S, Kawakami Y, Okuyama H. Interleukin-1 production by alveolar macrophages is decreased in smokers. Am Rev Respir Dis. 1989;140:397–402.

    Google Scholar 

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Hockertz, S., Emmendörffer, A., Scherer, G. et al. Acute effects of smoking and high experimental exposure to environmental tobacco smoke (ETS) on the immune system. Cell Biol Toxicol 10, 177–190 (1994). https://doi.org/10.1007/BF00757561

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