Prevention of Allergic Diseases

  • Leena von Hertzen
  • Tari Haahtela
Part of the Allergy Frontiers book series (ALLERGY, volume 5)

Accumulating evidence indicates that an environment rich in microbes in childhood reduces the risk of developing atopic disease in later life [1]. Along with urbanization, the perpetual coexistence of environmental microorganisms with man has been severely disturbed, with unexpected consequences. It has been elegantly shown that continuous stimulation of the innate immunity cells by commensals and saprophytes is necessary for the proper development and maintenance of mucosal homeostasis [2]. Such continuous stimulation of the immune system through the skin, respiratory tract and gut is thought to activate the regulatory network, which in turn seems to be decisive in the development of tolerance and in the prevention of inflammation associated with atopic conditions and harmful Th2 responses [3, 4].

Allergy and asthma epidemic still continues in many western countries [5], whereas in some other, less affluent areas, it may have only started [6, 7]. Numerous studies have provided evidence that allergen avoidance is not the right strategy to reverse the rising trends in asthma and allergy prevalence. Avoidance of inhalant allergens is difficult, often impossible, and the results from avoidance interventions have not been encouraging [8–10]. As to food antigens, excessive avoidance in early life can be harmful and prevent or weaken the development of regulatory mechanisms. Virtually, the only possibility to reduce the allergy burden in a population is to strengthen those mechanisms that are involved in the development and maintenance of tolerance. Patients must be treated, but the strategies to reduce the allergy burden should focus on prevention and preventive treatment. In this chapter, the development of tolerance in the context of environmental factors, and the means by which allergies might be reduced at the national level are discussed.


Allergic Disease Allergy Clin Immunol House Dust Atopic Disease World Allergy Organization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    von Hertzen L, Haahtela T (2006) Disconnection of man and the soil — reason for the asthma and atopy epidemic? J Allergy Clin Immunol 117:334–44CrossRefGoogle Scholar
  2. 2.
    Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R (2004) Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118:229–41PubMedCrossRefGoogle Scholar
  3. 3.
    van Oosterhout A, Bloksma N (2005) Regulatory T-lymphocytes in asthma. Eur Respir J 26:918–32PubMedCrossRefGoogle Scholar
  4. 4.
    Rook G, Adams V, Hunt J, Palmer R, Martinelli R, Brunet LR (2004) Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders. Springer Semin Immunol 25:237–55CrossRefGoogle Scholar
  5. 5.
    von Hertzen L, Haahtela T (2005) Signs of reversing trends in prevalence of asthma. Allergy 60:283–92CrossRefGoogle Scholar
  6. 6.
    Raukas-Kivioja A, Raukas E, Loit HM, Kiviloog J, Ronmark E, Larsson K, Lundback B (2003) Allergic sensitisation among adults in Tallin, Estonia. Clin Exp Allergy 33:1342–48PubMedCrossRefGoogle Scholar
  7. 7.
    Annus T, Riikjärv MA, Rahu K, Björksten B (2005) Modest increase in seasonal allergic rhinitis and eczema over 8 years among Estonian schoolchildren. Pediatr Allergy Immunol 16:315–20PubMedGoogle Scholar
  8. 8.
    Gotzsche PC, Johansen HK, Schmidt LM, Burr ML (2005) House dust mite control measures for asthma. The Cochrane Database of Systematic Reviews. The Cochrane Collaboration 3Google Scholar
  9. 9.
    Sheikh A, Hurwitz B (2003) House dust mite avoidance measures for perennial allergic rhinitis: a systematic review of efficacy. Br J Gen Pract 53:318–22PubMedGoogle Scholar
  10. 10.
    Kilburn S, Lasserson TJ, McKean M (2006) Pet allergen control measures for allergic asthma in children and adults. Cochrane Database Syst Rev 1Google Scholar
  11. 11.
    von Hertzen L, Haahtela T (2004) Asthma and atopy — the price of affluence? Allergy 59:124–37CrossRefGoogle Scholar
  12. 12.
    von Mutius E (2004) Influences in allergy: epidemiology and the environment. J Allergy Clin Immunol 113:373–79CrossRefGoogle Scholar
  13. 13.
    Björksten B, Dumitrascu D, Foucard T, Khetsuriani N, Khaitov R, Leja M, Lis G, Pekkanen J, Priftanji A, Riikjarv MA (1998) Prevalence of childhood asthma, rhinitis and eczema in Scandinavia and Eastern Europe. Eur Respir J 12:432–37PubMedCrossRefGoogle Scholar
  14. 14.
    von Hertzen LC, Mäkela MJ, Petäys T, Jousilahti P, Kosunen TU, Laatikainen T, Vartiainen E,Haahtela T (2006) Growing disparities in atopy between the Finns and the Russians — a comparison of two generations. J Allergy Clin Immunol 117:151–57CrossRefGoogle Scholar
  15. 15.
    Hanski I (2005) The Shrinking World: Ecological Consequences of Habitat Loss — Excellence in Ecology 14. International Ecology Institute: GermanyGoogle Scholar
  16. 16.
    Liu AH (2002) Endotoxin exposure in allergy and asthma: reconciling a paradox. J Allergy Clin Immunol 109:379–92PubMedCrossRefGoogle Scholar
  17. 17.
    Gehring U, Bolte G, Borte M, Bischof W, Fahlbusch B, Wichmann HE, Heinrich J (2001) Exposure to endotoxin decreases the risk of atopic eczema in infancy: a cohort study. J Allergy Clin Immunol 108:847–54PubMedCrossRefGoogle Scholar
  18. 18.
    Gisi U, Schkendel R, Schulin R, Standelman F, Sticker H (1997) Bodenökologie. Stuttgart: Georg Thieme VerlagGoogle Scholar
  19. 19.
    Sekar R, Pernthaler A, Pernthaler J, Warnecke F, Posch T, Amann R (2003) An improved protocol for quantification of freshwater Actinobacteria by fluorescence in situ hybridization. Appl Environ Microbiol 69:2928–35PubMedCrossRefGoogle Scholar
  20. 20.
    Glöckner F, Zaichikov E, Belkova N, Denissova L, Pernthaler J, Pernthaler A, Amann R (2000) Comparative 16S rRNA analysis of lake bacterioplankton reveals globally distributed phylogenetic clusters including an abundant group of actinobacteria. Appl Environ Microbiol 66:5053–65PubMedCrossRefGoogle Scholar
  21. 21.
    Balows A, Hausler WJ Jr, Herrmann KL, Shadomy HJ (eds) (1991) Manual of Clinical Microbiology. American Society for Microbiology: Washington DC, pp 222–224, 238–257Google Scholar
  22. 22.
    Waser M, Michels KB, Bieli C, Flöistrup H, Pershagen G, von Mutius E, Ege M, Riedler J, Schram-Bijkerk D, Brunekreef B, van Hage M, Lauener R, Braun-Fahrländer C (2007) Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe. Clin Exp Allergy 37:661–70PubMedCrossRefGoogle Scholar
  23. 23.
    Perkin MR, Strachan DP (2006) Which aspects of the farming lifestyle explain the inverse association with childhood allergy? J Allergy Clin Immunol 177:1374–81CrossRefGoogle Scholar
  24. 24.
    Riedler J, Braun-Fahrländer C, Eder W, Schreuer M, Waser M, Maisch S, Carr D, Schierl R, Nowak D, von Mutius E (2001) Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358:1129–33PubMedCrossRefGoogle Scholar
  25. 25.
    Radon K, Windststter D, Eckart J, Dressel H, Leitritz L, Reichert J, Schmid M, Praml G, Schosser M, von Mutius E, Nowak D (2004) Farming exposure in childhood, exposure to markers of infections and the development of atopy in rural subjects. Clin Exp Allergy 34:1178–83PubMedCrossRefGoogle Scholar
  26. 26.
    Wickens K, Lane JM, Fitzharris P, Siebers R, Riley G, Douwes J, Smith T, Crane J (2002) Farm residence and exposures and the risk of allergic diseases in New Zealand children. Allergy 57:1171–79PubMedCrossRefGoogle Scholar
  27. 27.
    Barnes M, Cullinan P, Athanasaki P, Macneill S, Hole AM, Harris J, Kalogeraki S, Chatzinikolau M, Drakonakis N, Bibaki-Liakou V, Newman Taylor AJ, Bibakis I (2001) Crete: does farming explain urban and rural differences in atopy? Clin Exp Allergy 31:1822–28PubMedCrossRefGoogle Scholar
  28. 28.
    Remes ST, Iivanainen K, Koskela H, Pekkanen J (2003) Which factors explain the lower prevalence of atopy amongst farmers' children? Clin Exp Allergy 33:427–34PubMedCrossRefGoogle Scholar
  29. 29.
    Roginski H, Fuquay JW, Fox PF (eds) (2003) Encyclopedia of Dairy Sciences. Academic Press: Cornwall, pp 1786–96Google Scholar
  30. 30.
    Chatzi L, Apostolaki G, Bibakis I, Skypala I, Bibaki-Liakou V, Tzanakis T, Kogevinas M, Cullinan P (2007) Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete. Thorax 62:677PubMedCrossRefGoogle Scholar
  31. 31.
    Wong GW, Ko FW, Hui DS, Fok TF, Carr D, von Mutius E, Zhong NS, Chen YZ, Lai CK (2004). Factors associated with difference in prevalence of asthmain children from three cities in China: multicentre epidemiological survey. BMJ 329:1–4CrossRefGoogle Scholar
  32. 32.
    Nja F, Nystad W, Carlsen L, Hetlevik O, Carlsen KH (2005) Effects of early intake of fruit or vegetables in relation to later asthma and allergic sensitization. Acta Pediatrica 94:147–54CrossRefGoogle Scholar
  33. 33.
    Romieu I, Varraso R, Avenel V, Leynaert B, Kauffmann F, Clavel-Chapelon F (2006) Fruit and vegetable intakes and asthma in the E3N study. Thorax 61:209–15PubMedCrossRefGoogle Scholar
  34. 34.
    Butland BK, Strachan DP, Anderson HR (1999) Fresh fruit intake and asthma symptoms in young British adults: confounding or effect modification by smoking? Eur Respir J 13:744–50PubMedCrossRefGoogle Scholar
  35. 35.
    von Hertzen L, Laatikainen T, Pitkänen T, Vlasoff T, Mäkelä MJ, Vartiainen E, Haahtela T (2007) Microbial content of drinking water in Finnish and Russian Karelia — implications for atopy prevalence. Allergy 62:288–92CrossRefGoogle Scholar
  36. 36.
    Cooper PJ, Chico ME, Rodriguest LC, Strachan DP, Anderson HR, Rodriguez EA, Gaus DP, Griffin GE (2004) Risk factors for atopy among school children in a rural area of Latin America. Clin Exp Allergy 34:845–52PubMedCrossRefGoogle Scholar
  37. 37.
    Haileamlak A, Dagoye D, Williams H, Venn AJ, Hubbard R, Britton J, Lewis SA (2005) Early life risk factors for atopic dermatitis in Ethiopian children. J Allergy Clin Immunol 1154:370–6CrossRefGoogle Scholar
  38. 38.
    Flohr C, Tuyen LN, Lewis S, Quinnell R, Minh TT, Liem HT, Campbell J, Pritchard D, Hien TT, Farrar J, Williams H, Britton J (2006) Poor sanitation and helminth infection protect against skin sensitisation in Vietnamese children: A cross-sectional study. J Allergy Clin Immunol 118:1305–11PubMedCrossRefGoogle Scholar
  39. 39.
    Boasen J, Chrishol D, Lebet L, Akira S, Horner AA (2005) House dust extract elicit Toll-like receptor-dependent dendritic cell responses. J Allergy Clin Immunol 116:185–91PubMedCrossRefGoogle Scholar
  40. 40.
    Hessle C, Andersson B, Wold AE (2000). Gram-positive bacteria are potent inducers of monocytic interleukin-12 (IL-12) while gram-negative bacteria preferentially stimulate IL-10 production. Infect Immun 68:3581–86PubMedCrossRefGoogle Scholar
  41. 41.
    Lindström ES, Bergström AK (2005) Community composition of bacterioplankton and cell transport in lakes in two different drainage areas. Aquat Sci 67:210–19CrossRefGoogle Scholar
  42. 42.
    Battaglia M, Gregori S, Bacchetta R, Roncarolo MG (2006) Tr1 cells: from discovery to their clinical application. Semin Immunol 18:120–27PubMedCrossRefGoogle Scholar
  43. 43.
    Feleszko W, Jaworska J, Hamelmann E (2006) Toll-like receptors — novel targets in allergic airway disease (probiotics, friends and relatives). Eur J Pharmacol 533:308–18PubMedCrossRefGoogle Scholar
  44. 44.
    Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987–95PubMedCrossRefGoogle Scholar
  45. 45.
    Gershon RK, Kondo K (1971) Infectious immunological tolerance. Immunology 21:903–14PubMedGoogle Scholar
  46. 46.
    Gershon RK, Cohen P, Hencin R, Liebhaber SA (1972) Suppressor T cells. J Immunol 108:585–90Google Scholar
  47. 47.
    Romagnani S (2006) Regulation of the T cell response. Clin Exp Allergy 36:1357–66PubMedCrossRefGoogle Scholar
  48. 48.
    Umetsu D, DeKruyff R (2006) The regulation of allergy and asthma. Immunol Rev 212:238–55PubMedCrossRefGoogle Scholar
  49. 49.
    Harylowicz CM, O'Garra A (2005) Potential role of interleukin-10 — secreting regulatory T cells in allergy and asthma. Nat Rev Immunol 5:271–83CrossRefGoogle Scholar
  50. 50.
    Vigouroux S, Yvon E, Biagi E, Brenner M (2004) Antigen-induced regulatory T cells. Blood 104:26–33PubMedCrossRefGoogle Scholar
  51. 51.
    Robinson DS, Larche M, Durham SR (2004) T regs and allergic diseases. J Clin Invest 114:1389–97PubMedGoogle Scholar
  52. 52.
    Umetsu DT, Akbari O, DeKruyff RH (2003) Regulatory T cells control the development of allergic disease and asthma. J Allergy Clin Immunol 112:480–87PubMedCrossRefGoogle Scholar
  53. 53.
    Mills KHG (2004) Regulatory T cells: friend or foe in immunity to infection? Nat Rev Immunol 4:841–55PubMedCrossRefGoogle Scholar
  54. 54.
    Platts-Mills TAE, Woodfolk JA, Erwin EA, Aalberse R (2004) Mechanisms of tolerance to inhalant allergens: the relevance of a modified Th2 response to allergens from domestic animals. Springer Semin Immun 25:271–79CrossRefGoogle Scholar
  55. 55.
    Platts-Mills T (2007) The role of indoor allergens in chronic allergic disease. Presented at the World Immune Regulation Meeting, 11–15 April, Davos, Switzerland, Abstr: 26Google Scholar
  56. 56.
    Braun-Fahrländer C, Riedler J, Herz U, Eder W, Waser M, Grize L, Maisch S, Carr D, Gerlach F, Bufe A, Lauener RP, Schierl R, Renz H, Nowak D, von Mutius E (2002) Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 347:869–77PubMedCrossRefGoogle Scholar
  57. 57.
    Iossifova YY, Reponen T, Bernstein DI, Levin L, Kaira H, Campo P, Villareal M, Lockey J, Hershey GK, LeMasters G (2007) House dust (1-3)- β -D-glucan and wheezing in infants. Allergy 62:504–13PubMedCrossRefGoogle Scholar
  58. 58.
    Custovic A, Hallam CL, Simpson BM, Craven M, Smpson A, Woodcock A (2001) Deacreased prevalence of sensitisation to cats with high exposure to cat allergen. J Allergy Clin Immunol 108:537–39PubMedCrossRefGoogle Scholar
  59. 59.
    Cullinan P, MacNeill SJ, Harris JM, Moffat S, White C, Mills P, Newman Taylor AJ (2004) Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study. Thorax 59:855–61PubMedCrossRefGoogle Scholar
  60. 60.
    Jeal H, Draper A, Harris J, Taylor AN, Cullinan P, Jones M (2006) Modified Th2 responses at high-dose exposures to allergen — using an occupational model. Am J Respir Crit Care Med 174:21–25PubMedCrossRefGoogle Scholar
  61. 61.
    Matsui EC, Eggleston PA, Breysse PN, Rand CS, Diette GB (2007) Mouse-allergen-specific antibody responses in inner-city children with asthma. J Allergy Clin Immunol 119:910–15PubMedCrossRefGoogle Scholar
  62. 62.
    Pacheo KA (2007) New insights into laboratory animal exposures and allergic responses. Curr Opin Allergy Clin Immunol 7:156–61CrossRefGoogle Scholar
  63. 63.
    Holt PG, Thomas WR (2005) Sensitization to airborne environmental allergens: unresolved issues. Nat Immunol 6:957–60PubMedCrossRefGoogle Scholar
  64. 64.
    Schram-Bijkerk D, Doekes G, Boeve M, Douwes J, Riedler J, Üblagger E, von Mutius E, Budde J, Pershagen G, van Hage M, Wickman M, Braun-Fahrländer C, Waser M, Brunekreef B (2006) A non-linear relation between mite allergen levels and sensitisation in farm and nonfarm children. Allergy 61:640–47PubMedCrossRefGoogle Scholar
  65. 65.
    Yazdanbakhsh M, Wahyuni S (2005) The role of helminth infections in protection from atopic disorders. Curr Opin Allergy Clin Immunol 5:386–91PubMedCrossRefGoogle Scholar
  66. 66.
    Simpson A, Custovic A (2003) Early pet exposure: friend or foe? Curr Opin Allergy Immunol 3:7–14CrossRefGoogle Scholar
  67. 67.
    Pakarinen J, Hyvärinen A, Salkinoja-Salonen M, Laitinen S, Nevalainen A, Mäkelä MJ, Haahtela T, von Hertzen L The predominance of Gram-positive bacteria in house dust in the low-allergy risk Russian Karelia. Environ Microbiol 2008;10:3317–25PubMedCrossRefGoogle Scholar
  68. 68.
    Heumann D, Barras C, Severin A, Glauser MP, Tomasz A (1994) Gram-positive cell walls stimulate synthesis of tumour necrosis factor alpha and interleukin-6 by human monocytes. Infect Immun 62:2715–21PubMedGoogle Scholar
  69. 69.
    De Kimpe S, Kengatharan M, Thiemermann C, Vane J (1995) The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure. Proc Natl Acad Sci USA 92:10359–63PubMedCrossRefGoogle Scholar
  70. 70.
    Kirsching CJ, Schumann RR (2002) TLR2: cellular sensor for microbial and endogenous molecular patterns. Curr Top Microbiol Immunol 270:21–44Google Scholar
  71. 71.
    Travassos LH, Girardin SE, Philpott DJ, Blanot D, Nahori MA, Werts C, Boneca IG. (2004) Toll-like receptor 2 — dependent bacterial sensing does not occur via peptidoglycan recognition. EMBO Reports 5:1000–06PubMedCrossRefGoogle Scholar
  72. 72.
    Boneca IG (2005) The role of peptidoglycan in pathogenesis. Curr Opin Microbiol 8:46–53PubMedCrossRefGoogle Scholar
  73. 73.
    Heine H, Lien E (2003) Toll-like receptors and their function in innate and adaptive immunity. Int Arch Allergy Immunol 130:180–92PubMedCrossRefGoogle Scholar
  74. 74.
    Girardin SE, Philpott DJ, Lemaitre B (2003) Sensing microbes by diverse hosts. EMBO Reports 4:932–36PubMedCrossRefGoogle Scholar
  75. 75.
    Brown GD, Herre J, Williams DL, Willment JA, Marshall AS, Gordon S (2003) Dectin-1 mediates the biological effect of β -glucans. J Exp Med 197:1119–24PubMedCrossRefGoogle Scholar
  76. 76.
    Gantner BN, Simmons RM, Canavera SI, Akira S, Underhill DM (2003) Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med 197:1107–17PubMedCrossRefGoogle Scholar
  77. 77.
    Re F, Strominger JL (2004) IL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cells. J Immunol 173:7548–55PubMedGoogle Scholar
  78. 78.
    Sutmuller RPM, den Brok MH, Kramer M, Bennink EJ, Toonen LW, Kullberg BJ, Joosten LA, Akira S, Netea MG, Adema GJ (2006) Toll-like receptor 2 controls expansion and function of regulatory T cells. J Clin Invest 116:485–94PubMedCrossRefGoogle Scholar
  79. 79.
    Taylor R, Richmond P, Upham JW (2006) Toll-like receptor 2 ligands inhibit Th2 responses to mite allergen. J Allergy Clin Immunol 117:1148–54PubMedCrossRefGoogle Scholar
  80. 80.
    Moseman EA, Liang X, Dawson AJ, Panoskaltsis-Mortari A, Krieg AM, Liu YJ, Blazar BR, Chen W (2004) Human plasmacytoid dendritic cells activated by CpG oligonucleotides induce the generation of CD4+CD25+ regulatory T cells. J Immunol 173:4433–42PubMedGoogle Scholar
  81. 81.
    Bashir ME, Louie S, Shi HN, Nagler-Anderson C (2004) Toll-like receptor 4 signalling intestinal microbes influences susceptibility to food allergy. J Immunol 172:6978–87PubMedGoogle Scholar
  82. 82.
    Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA (2006) Mechanisms of immune suppression by interleukin-10 and transforming growth factor- β: the role of T regulatory cells. Immunology 117:433–42PubMedCrossRefGoogle Scholar
  83. 83.
    O'Garra A, Vieira P (2004) Regulatory T cells and mechanisms of immune system control. Nat Med 10:801–05PubMedCrossRefGoogle Scholar
  84. 84.
    Liu H, Komai-Koma M, Xu D, Liew FY (2006) Toll-like receptor 2 signalling modulates the functions of CD4+CD25+ regulatory T cells. Proc Natl Acad Sci USA 103:7048–53PubMedCrossRefGoogle Scholar
  85. 85.
    Lauener RP, Birchler T, Adamski J, Braun-Fahrländer C, Bufe A, Herz U, von Mutius E, Nowak D, Riedler J, Waser M, Sennhauser FH (2002) Expression of CD14 and Toll-like receptor 2 in farmers' and non-farmers' children. Lancet 360:465–6PubMedCrossRefGoogle Scholar
  86. 86.
    Eder W, Klimecki W, Yu L, von Mutius E, Riedler J, Braun-Fahrländer C, Nowak D, Martinez FD (2004) Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol 113:482–88PubMedCrossRefGoogle Scholar
  87. 87.
    Martinez FD (2007) Genes, environment, development and asthma: a reappraisal. Eur Respir J 29:179–84PubMedCrossRefGoogle Scholar
  88. 88.
    Cario E, Gerken G, Podolsky DK (2007) Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology 132:1359–74PubMedCrossRefGoogle Scholar
  89. 89.
    Lambrecht BN (2005) Denritic cells and the regulation of the allergic immune response. Allergy 60:271–82PubMedCrossRefGoogle Scholar
  90. 90.
    Tourney KG, van Hove C, Grooten J, Moerloose K, Brusselle GG, Joos GF (2006) Animal models of allergen-induced tolerance in asthma: are T-regulatory-1 cells (Tr-1) the solution for T-helper-2 cells (Th-2) in asthma? Clin Exp Allergy 36:8–20CrossRefGoogle Scholar
  91. 91.
    Kaisho T, Akira K (2006) Toll-like receptor function and signalling. J Allergy Clin Immunol 117:979–87PubMedCrossRefGoogle Scholar
  92. 92.
    Bird AP, Taggart MH (1980) Variable patterns of total DNA and rDNA methylation in animals. Nucleic Acids Res 8:1485–97PubMedCrossRefGoogle Scholar
  93. 93.
    Antequera F, Tamame M, Villanueva JR, Santos T (1984) DNA methylation in the fungi. J Biol Chem 259:8033–36PubMedGoogle Scholar
  94. 94.
    de Heer HJ, Hammad H, Soullie T, Hijdra D, Vos N, Willart AM, Hoogssteden C, Lambrecht BN (2004) Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 200:89–98PubMedCrossRefGoogle Scholar
  95. 95.
    Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, Thunberg S, Deniz G, Schmidt-Weber C, Blaser K, Akdis CA (2004) Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 199:1567–75PubMedCrossRefGoogle Scholar
  96. 96.
    Akdis M, Akdis CA (2006) Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol 119:780–89CrossRefGoogle Scholar
  97. 97.
    Ling EM, Smith T, Nguyen D, Pridgeon C, Dallman M, Arbery J, Carr VA, Robinson DS (2004) Relation of CD4+CD25+ regulatory T cell suppression of allergen-driven T cell activation to atopic status and expression of allergic disease. Lancet 363:608–15PubMedCrossRefGoogle Scholar
  98. 98.
    Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis CA (2003) IL-10 and TGF- β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 33:1205–14PubMedCrossRefGoogle Scholar
  99. 99.
    Sun-Payer E, Cantor H (2001) Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4+CD25+ T cells. J Autoimmun 16:115–23CrossRefGoogle Scholar
  100. 100.
    Pham-Thi N, de Blic J, Scheinmann P (2006) Sublingual immunotherapy in the treatment of children. Allergy 61(Suppl 81):7–10PubMedCrossRefGoogle Scholar
  101. 101.
    Johansson SGO, Haahtela T (2004) World Allergy Organization Guidelines for prevention of allergy and allergic asthma. Int Arch Allergy Immunol 135:83–92PubMedCrossRefGoogle Scholar
  102. 102.
    Bousquet J, Anto JM, Bachert C, Bousquet PJ, Colombo P, Crameri R, Daëron M, Fokkens W, Leynaert B, Lahoz C, Maurer M, Passalacqua G, Valenta R, van Hage M, van Ree R (2006) Factors responsible for differences between asymptomatic subjects and patients presenting an IgE sensitisation to allergens. A GA2LEN project. Allergy 61:671–80Google Scholar
  103. 103.
    Vartiainen E, Petäys T, Haahtela T, Jousilahti P, Pekkanen J (2002) Allergic diseases, skin prick test responses and IgE levels in North Karelia, Finland, and the Republic of Karelia, Russia. J Allergy Clin Immunol 109:643–48PubMedCrossRefGoogle Scholar
  104. 104.
    Kalliomäki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E (2001) Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 357:1057–59CrossRefGoogle Scholar
  105. 105.
    Taylor AL, Dunstan JA, Prescott SL (2007) Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitisa-tion in high-risk children: a randomised controlled trial. J Allergy Clin Immunol 119:184–91PubMedCrossRefGoogle Scholar
  106. 106.
    Helin T, Haahtela S, Haahtela T (2002) No effect of oral treatment with an intestinal bacterial strain, Lactobacillus rhamnosus (ATCC53103), on birch-pollen allergy: a placebo-controlled double-blind study. Allergy 57:243–46PubMedCrossRefGoogle Scholar
  107. 107.
    Kukkonen K, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Kuitunen M (2007) Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 119:192–98PubMedCrossRefGoogle Scholar
  108. 108.
    Abrahamsson TR, Jacobsson T, Bottcher MF, Fredrikson M, Jenmalm MC, Bjorksten B, Oldaeus G (2007) probiotics in prevention of IgE-associated eczema: a double-blind, randomised, placebo-controlled trial. J Allergy Clin Immunol 119:1174–80PubMedCrossRefGoogle Scholar
  109. 109.
    Latvala J, von Hertzen L, Lindholm H, Haahtela T (2005) Trends in prevalence of asthma and allergy in Finnish young men: a nationwide study from 1966 to 2003. BMJ 330:1186–87PubMedCrossRefGoogle Scholar
  110. 110.
    Haahtela T, Tuomisto LE, Pietinalho A, Klaukka T, Erhola M, Kaila M, Nieminen MM, Kontula E, Laitinen LA (2006) A 10-year asthma programme in Finland: major change for the better. Thorax 61:663–70PubMedCrossRefGoogle Scholar
  111. 111.
    Haahtela T, von Hertzen L, Mäkelä M, Hannuksela M (2008) The Allergy Programme Working Group. Finnish Allergy Programme 2008–2018 — time to act and change the course. Allergy 63:634–45PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Leena von Hertzen
    • 1
  • Tari Haahtela
    • 1
  1. 1.Skin and Allergy Hospital/ HUCHFinland

Personalised recommendations