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. 1999 Jun;107(Suppl 3):485–487. doi: 10.1289/ehp.99107s3485

Potential role of environmental factors in the etiology and pathogenesis of atopy: a working model.

P G Holt 1
PMCID: PMC1566234  PMID: 10346996

Abstract

Sensitization to inhalant allergens commonly commences in utero, and most children are born with weak T helper-2 (Th2)-polarized T-cell immunity to these agents. During early life, these responses are normally deviated toward the Th1 cytokine profile. However, in atopics this immune deviation process fails, leading instead to consolidation of allergen-specific Th2 immunity and its eventual active expression in the airways. Both the induction and expression of Th2 immunity can be modulated by environmental agents that affect the cytokine milieu in the airway mucosa and/or the draining lymph nodes. Because of the known effects of the mold cell wall component (1-->3)-ss-d-glucan on monocyte cytokine secretion, exposure to molds during childhood may be a significant etiologic factor in allergic respiratory disease in general.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson H. R. Air pollution and trends in asthma. Ciba Found Symp. 1997;206:190–207. [PubMed] [Google Scholar]
  2. Di Luzio N. R. Update on the immunomodulating activities of glucans. Springer Semin Immunopathol. 1985;8(4):387–400. doi: 10.1007/BF01857392. [DOI] [PubMed] [Google Scholar]
  3. Holt P. G., Macaubas C. Development of long-term tolerance versus sensitisation to environmental allergens during the perinatal period. Curr Opin Immunol. 1997 Dec;9(6):782–787. doi: 10.1016/s0952-7915(97)80178-1. [DOI] [PubMed] [Google Scholar]
  4. Holt P. G., Sly P. D., Björkstén B. Atopic versus infectious diseases in childhood: a question of balance? Pediatr Allergy Immunol. 1997 May;8(2):53–58. doi: 10.1111/j.1399-3038.1997.tb00145.x. [DOI] [PubMed] [Google Scholar]
  5. Johnston S. L., Pattemore P. K., Sanderson G., Smith S., Campbell M. J., Josephs L. K., Cunningham A., Robinson B. S., Myint S. H., Ward M. E. The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis. Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):654–660. doi: 10.1164/ajrccm.154.3.8810601. [DOI] [PubMed] [Google Scholar]
  6. McWilliam A. S., Napoli S., Marsh A. M., Pemper F. L., Nelson D. J., Pimm C. L., Stumbles P. A., Wells T. N., Holt P. G. Dendritic cells are recruited into the airway epithelium during the inflammatory response to a broad spectrum of stimuli. J Exp Med. 1996 Dec 1;184(6):2429–2432. doi: 10.1084/jem.184.6.2429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Michel O., Nagy A. M., Schroeven M., Duchateau J., Nève J., Fondu P., Sergysels R. Dose-response relationship to inhaled endotoxin in normal subjects. Am J Respir Crit Care Med. 1997 Oct;156(4 Pt 1):1157–1164. doi: 10.1164/ajrccm.156.4.97-02002. [DOI] [PubMed] [Google Scholar]
  8. Nemoto J., Ohno N., Saito K., Adachi Y., Yadomae T. Expression of interleukin 1 family mRNAs by a highly branched (1-->3)-beta-D-glucan, OL-2. Biol Pharm Bull. 1993 Oct;16(10):1046–1050. doi: 10.1248/bpb.16.1046. [DOI] [PubMed] [Google Scholar]
  9. Poulter L. W., Janossy G., Power C., Sreenan S., Burke C. Immunological/physiological relationships in asthma: potential regulation by lung macrophages. Immunol Today. 1994 Jun;15(6):258–261. doi: 10.1016/0167-5699(94)90004-3. [DOI] [PubMed] [Google Scholar]
  10. Prescott S. L., Macaubas C., Holt B. J., Smallacombe T. B., Loh R., Sly P. D., Holt P. G. Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile. J Immunol. 1998 May 15;160(10):4730–4737. [PubMed] [Google Scholar]
  11. Prescott S. L., Macaubes C., Yabuhara A., Venaille T. J., Holt B. J., Habre W., Loh R., Sly P. D., Holt P. G. Developing patterns of T cell memory to environmental allergens in the first two years of life. Int Arch Allergy Immunol. 1997 May-Jul;113(1-3):75–79. doi: 10.1159/000237512. [DOI] [PubMed] [Google Scholar]
  12. Romagnani S. Induction of TH1 and TH2 responses: a key role for the 'natural' immune response? Immunol Today. 1992 Oct;13(10):379–381. doi: 10.1016/0167-5699(92)90083-J. [DOI] [PubMed] [Google Scholar]
  13. Rylander R., Holt P. G. (1-->3)-beta-D-glucan and endotoxin modulate immune response to inhaled allergen. Mediators Inflamm. 1998;7(2):105–110. doi: 10.1080/09629359891252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rylander R., Norrhall M., Engdahl U., Tunsäter A., Holt P. G. Airways inflammation, atopy, and (1--> 3)-beta-D-glucan exposures in two schools. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1685–1687. doi: 10.1164/ajrccm.158.5.9712139. [DOI] [PubMed] [Google Scholar]
  15. Thepen T., McMenamin C., Girn B., Kraal G., Holt P. G. Regulation of IgE production in pre-sensitized animals: in vivo elimination of alveolar macrophages preferentially increases IgE responses to inhaled allergen. Clin Exp Allergy. 1992 Dec;22(12):1107–1114. doi: 10.1111/j.1365-2222.1992.tb00137.x. [DOI] [PubMed] [Google Scholar]
  16. Wegmann T. G., Lin H., Guilbert L., Mosmann T. R. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today. 1993 Jul;14(7):353–356. doi: 10.1016/0167-5699(93)90235-D. [DOI] [PubMed] [Google Scholar]
  17. Wierenga E. A., Snoek M., de Groot C., Chrétien I., Bos J. D., Jansen H. M., Kapsenberg M. L. Evidence for compartmentalization of functional subsets of CD2+ T lymphocytes in atopic patients. J Immunol. 1990 Jun 15;144(12):4651–4656. [PubMed] [Google Scholar]
  18. Yabuhara A., Macaubas C., Prescott S. L., Venaille T. J., Holt B. J., Habre W., Sly P. D., Holt P. G. TH2-polarized immunological memory to inhalant allergens in atopics is established during infancy and early childhood. Clin Exp Allergy. 1997 Nov;27(11):1261–1269. [PubMed] [Google Scholar]

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