Abstract
Some have suggested that tobacco smoke may skew the immune system toward a Th2 pattern, however the effects of genetics or childhood exposures could explain these results. We compared PMBC supernatant or serum Th1 (INF-γ) and Th2 (IL-4, IL-5, and IL-13) cytokine and IgE levels in members of 45 pairs of nonasthmatic monozygotic twins with varying levels of current cigarette consumption to determine if smoking was associated with Th1/Th2 function after accounting for genetic factors. A statistically significant dose-response was observed between levels of smoking and IL-13 (p=0.05). Mean IL-13 level among heavy smokers (20+ cigarettes/day) was 146% higher than that among nonsmokers (+26.2 pg/mL; p=0.04). The mean IL-5 level among heavy smokers was 166% higher than that among light (<20 cigarettes/day) smokers (+3.4 pg/mL; p=0.03). No statistically significant differences in INF-γ, IL-4, or IgE levels were observed. Smoking appears to be associated with increased levels of IL-13.
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Strachan DP, Butland BK, Anderson HR: Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort. BMJ312:1195–1199, 1996
Vesterinen E, Kaprio J, Kiskenvuo M: Prospective study of asthma in relation to smoking habits among 14,729 adults. Thorax43:534–539, 1998
Ulrik CS, Frederiksen J: Mortality and markers of risk of asthma among 1075 outpatients with asthma. Chest108:10–15, 1995
Kuschner WG, D’Alessandro A, Wong H, Blanc PD: Dose-dependent cigarette smoking-related inflammatory responses in healthy adults. Eur Respir J9:1989–1994, 1996
Li XY, Rahman I, Donaldson K, MacNee W: Mechanisms of cigarette smoke induced increased airspace permeability. Thorax51:465–471, 1996
Jones JG, Lawler P, Crawley JCW, Minty BD, Hulands G, Neall N: Increased alveolar epithelial permeability in cigarette smokers. Lancet i:66–68, 1980
Gern JE, Lemanske RF, Jr, Busse WW: Early life origins of asthma. J Clin Invest104:837–843, 1999
Byron KA, Varigos GA, Wootton AM: IL-4 production is increased in cigarette smokers. Clin Exp Immunol95:333–336, 1994
Noakes PS, Holt PG, Prescott SL: Maternal smoking in pregnancy alters neonatal cytokine responses. Allergy58:1053–1058, 2003
Cockburn M, Hamilton A, Zadnick J, Cozen W, Mack T: Development and representativeness of a large population-based cohort of native California twins. Twin Res4:242–250, 2001
Macy E, Kemeny DM, Saxon A: Enhanced ELISA: How to measure less than 10 picograms of a specific protein (immunoglobulin) in less than 8 hours. FASEB J 2:3003, 1998
Conover WJ, Iman RL: Analysis of covariance using the rank transformation. Biometrics38:715–724, 1982
Tsunoda M, Litonjua AA, Kuniak MP, Weiss ST, Satoh T, Guevarra L, Tollerud DJ: Serum cytokine levels, cigarette smoking and airway responsiveness among pregnant women. Int Arch Allergy Immunol130:158–164, 2003
Hagiwara E, Takahashi KI, Okubo T, Ohno S, Ueda A, Aoki A, Odagiri S, Ishigatsubo Y: Cigarette smoking depletes cells spontaneously secreting Th (1) cytokines in the human airway. Cytokine14:121–126, 2001
Fischer A, Konig W: Modulation of in vitro immunoglobulin synthesis of human peripheral blood mononuclear cells by nicotine and cotinine. Clin Invest72:225–232, 1994
Le Cam L, Lagier B, Bousquet J, Pene J: Nicotine does not modulate IL-4 and Interferon-γ release from peripheral blood mononuclear cells and T cell clones activated by phorbol myristate acetate and calcium ionophore. Int Arch Allergy Immunol111:372–375, 1996
Arima K, Umeshita-Suyama R, Sakata Y, Akaiwa M, Mao XQ, Enomoto T, Dake Y, Shimazu S, Yamashita T, Sugawara N, Brodeur S, Geha R, Puri RK, Sayegh MH, Adra CN, Hamasaki N, Hopkin JM, Shirakawa T, Izuhara K: Upregulation of IL-13 concentration in vivo by the IL-13 variant associated with bronchial asthma. JACI109:980–987, 2002
Marsh DG, Neely JD, Ghosh IR, Freidhoff E, Ehrlich-Kautzky G, Krishnaswamy G: Linkage analysis of IL-4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science264:1152–1156, 1994
Burrows B, Halonen M, Barbee RA, Lebowitz MD: The relationship of serum immunoglobulin E to cigarette smoking. Am Rev Respir Dis124:523–525, 1981
Bahna SL, Heiner DC, Myhre BA: Immunoglobulin E pattern in cigarette smokers. Allergy38:57–64, 1983
Jarvis D, Chinn S, Luczynska C, Burney P: The association of smoking with sensitization to common environmental allergens: Results from the European Community Respiratory Health Survey. J Allergy Clin Immunol104:934–940, 1999
Oryszczyn MP, Annesi I, Neukirch F, Dore MF, Kauffmann F: Longitudinal observations of serum IgE and skin prick test response. Am J Respir Crit Care Med151:663–668, 1995
Husby S, Holm NV, Christensen K, Skov R, Morling N, Petersen PH: Cord blood immunoglobulin E in like-sexed monozygotic and dizygotic twins. Clin Genet50:332–338, 1996
Strachan DP, Wong J, Spector TD: Concordance and interrelationship of atopic diseases and markers of allergic sensitization among adult female twins. J Allergy Clin Immunol108:901–907, 2001
Hanson B, BcGue M, Roitman-Johnson, B. Segal NL, Bourchard TJ, Blumenthal MN: Atopic disease and immunoglobulin E in twins reared apart and reared together. Am J Hum Genet48:873–879, 1991
Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, Donaldson DD: Interleukin-13: Central mediator of allergic asthma. Science282:2258–2261, 1998
Seymour BW, Pinkerton KE, Friebertshauser KE, Coffman RL, Gershwin LJ: Second-hand smoke is an adjuvant for T helper-2 responses in a murine model of allergy. J Immunol159:6169–6175, 1997
Rumold R, Jyrala M, Diaz-Sanchez D: Secondhand smoke induces allergic sensitization in mice. J Immunol167:4765–4770, 2001
Whitekus MK, Li N, Zhang M, Wang M, Horwitz MA, Nelson SK, Horwtiz LD, Brechun N, Diaz-Sanchez D, Nel AE: Thiol antioxidants inhibit the adjuvant effects of aerosolized diesel exhaust particles in a murine model for ovalbumin sensitization. J Immunol168:2560–2567, 2002
Schmid-Grendelmeier P, Altznauer F, Fischer B, Bizer C, Straumann A, Menz G, Blaser K, Wuthrich B, Simon HU: Eosinophils express functional IL-13 in eosinophilic inflammatory diseases. J Immunol169:1021–1027, 2002
Wynn TA: IL-13 effector functions. Ann Rev Immunol21:425–456, 2003
Ohshima Y, Yasutomi M, Omata N, Yamada A, Fujisawa K, Kasuga K, Hiraoka M, Mayumi M: Dysregulation of IL-13 production by cord blood CD4+ T cells is associated with the subsequent development of atopic disease in infants. Pediatr Res 51:195–200, 2002
Schreiber GH, Schreiber RD: Interferon-γ. In The Cytokine Handbook, AW Thomson, MT Lotze (eds). London, Academic Press, 2003, pp 567–603
Hayden C, Pereira E, Rye P, Palmer L, Gibson N, Palenque M, Hagel I, Lynch N, Goldblatt J, Lesouef P: Mutation screening of interferon-gamma (INFγ) as a candidate gene for asthma. Clin Exp Allergy27:1412–1416, 1997
Graves PE, Kabesch M, Halonen M, Holberg CJ, Baldini M, Fritzsch C, Weiland SK, Erickson RP, von Mutius E, Martinez FD: A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children. J Allergy Clin Immunol105:506–513, 2000
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COZEN, W., DIAZ-SANCHEZ, D., JAMES GAUDERMAN, W. et al. Th1 and Th2 Cytokines and IgE Levels in Identical Twins with Varying Levels of Cigarette Consumption. J Clin Immunol 24, 617–622 (2004). https://doi.org/10.1007/s10875-004-6247-0
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DOI: https://doi.org/10.1007/s10875-004-6247-0