Skip to main content
SpringerLink
Log in

The Use of Cytokines in the Identification and Characterization of Chemical Allergens

  • Protocol
Cytokines in Human Health

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

  • 804 Accesses

Abstract

Many chemicals cause skin sensitization, resulting in allergic contact dermatitis, a delayed type hypersensitivity reaction. Chemical respiratory allergy is also an important occupational health problem, but there are currently available no validated methods for hazard identification, partly because of the fact that the relevant cellular and molecular mechanisms of sensitization of the respiratory tract have been unclear, with particular controversy regarding an obligatory role for IgE. Increasing evidence now exists that respiratory sensitization is associated with the preferential activation of type 2 T-lymphocytes and the expression of type 2 cytokines interleukin (IL)-, IL-5, IL-10, and IL-13. Type 2 cell products favor immediate type hypersensitivity reactions, serving as growth and differentiation factors for mast cells and eosinophils, the cellular effectors of the clinical manifestations of the allergic responses, and promoting IgE antibody production. In contrast, chemical contact allergens induce type 1 cytokine expression profiles. There has been considerable interest in the application of cytokine profiling for the characterization of chemical allergens, with cytokine phenotypes analyzed in freshly isolated tissue, or after culture in the presence or absence of mitogen at the level of protein secretion or messenger ribonucleic acid expression. The most common configuration of cytokine profiling, measurement of induced cytokine secretion patterns in the absence of restimulation, shows considerable promise as an approach for the identification and characterization of chemical respiratory allergens.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cronin E. Contact Dermatitis. London: Churchill Livingstone; 1980.

    Google Scholar 

  2. Chan-Yeung M, Malo JL. Compendium 1. Table of major inducers of occupational asthma. In: Bernstein IL, Chan-Yeung M, Malo JL, et al, eds. Asthma in the Workplace. New York: Marcel Dekker; 1993, pp. 595–623.

    Google Scholar 

  3. Magnusson B, Kligman AM. Allergic Contact Dermatitis in the Guinea Pig. Springfield, IL: Charles C. Thomas; 1970.

    Google Scholar 

  4. Buehler EV. (1965). Delayed contact hypersensitivity in the guinea pig. Arch Dermatol 1965;91:171–177.

    Article  CAS  PubMed  Google Scholar 

  5. Kimber I, Basketter DA. The murine local lymph node assay: a commentary on collaborative studies and new directions. Food Chem Toxicol 1992;30:165–169.

    Article  CAS  PubMed  Google Scholar 

  6. Kimber I, Bernstein IL, Karol MH, Robinson MK, Sarlo K, Scigrade MK. Identification of respiratory allergens. Fundam Appl Toxicol 1996;33:1–10.

    Article  CAS  PubMed  Google Scholar 

  7. Karol MH, Stadler J, Magreni C. Immunotoxicologic evaluation of the respiratory system: animal models for immediate and delayed-onset pulmonary hypersensitivity. Fundam Appl Toxicol 1985;5:459–472.

    Article  CAS  PubMed  Google Scholar 

  8. Pauluhn J. Predictive testing for respiratory sensitization. Toxicol Lett 1996;86:177–185.

    Article  CAS  PubMed  Google Scholar 

  9. Sarlo K, Ritz HL. Predictive assessment of respiratory sensitizing potential in guinea pigs. In: Kimber I, Dearman RJ, ed. Toxicology of Chemical Respiratory Hypersensitivity. London: Taylor and Francis; 1997, pp. 107–120.

    Google Scholar 

  10. Dearman RJ, Basketter DA, Coleman JW, Kimber I. The cellular and molecular basis for divergent allergic responses to chemicals. Chem-Biol Interact 1992;84:1–10.

    Article  CAS  PubMed  Google Scholar 

  11. Kimber I, Dearman RJ. Cell and molecular biology of chemical allergy. Clin Rev Allergy Immunol 1997; 15:145–168.

    Article  CAS  PubMed  Google Scholar 

  12. Mapp C, Boschetto P, Miotto D, De Rosa E, Fabbri LM. Mechanisms of occupational asthma. Ann Allergy Asthma Immunol 1999; 83:645–664.

    Article  CAS  PubMed  Google Scholar 

  13. Bendelac A, Schwartz RH. ThO cells in the thymus. The question of T-helper lineages. Immunol Rev 1991;123:169–188.

    Article  CAS  PubMed  Google Scholar 

  14. Sad S, Marcotte R, Mosmann TR. Cytokine-induced differentiation of precursor mouse CD8+ T cells into cytotoxic CD8+T cells secreting Th1 or Th2 cytokines. Immunity 1995;2:271–279.

    Article  CAS  PubMed  Google Scholar 

  15. Mosmann TR, Sad S. The expanding universe of T cell subsets: Th1, Th2 and more. Immunol Today 1996;17:138–146.

    Article  CAS  PubMed  Google Scholar 

  16. Romagnani S. Human ThI and Th2 subsets: doubt no more. Immunol Today 1991;12:256–257.

    Article  CAS  PubMed  Google Scholar 

  17. Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature 1996;383:787–793.

    Article  CAS  PubMed  Google Scholar 

  18. O’Garra A. Cytokines induce the development of functionally heterogenous T helper subsets. Immunity 1998;8:275–283.

    Article  CAS  Google Scholar 

  19. Romagnani S. T-cell subsets (Th1 versus Th2). Ann Allergy Asthma Immunol 2000; 85:9–18.

    Article  CAS  PubMed  Google Scholar 

  20. Bucy RP, Karr L, Huang GQ, et al. Single cell analysis of cytokine gene coexpression during CD4+ T-cell phenotype development. Proc Natl Acad Sci USA 1995;92:7565–7569.

    Article  CAS  PubMed  Google Scholar 

  21. Kelso A. Th1 and Th2 subsets: paradigms lost? Immunol Today 1995; 16:374–379.

    Article  CAS  PubMed  Google Scholar 

  22. Cher DJ, Mosmann TR. Two types of murine helper T cell clones. II. Delayed type hypersensitivity is mediated by Th1 clones. J Immunol 1987; 138:3688–3694.

    CAS  PubMed  Google Scholar 

  23. Diamantstein T, Eckert R, Volk HD, Kuper-Weglinski JW. Reversal by interferon-γ of inhibition of delayed-type hypersensitivity induction by anti-CD4 or anti-interleukin 2 receptor (CD25) monoclonal antibodies. Evidence for the physiological role of the CD4+Th1+ subset in mice. Eur J Immunol 1988; 181:2101–2103.

    Article  Google Scholar 

  24. Gorbachev AV, Fairchild RL. Induction and regulation of T-cell priming for contact hypersensitivity. Crit Rev Immunol 2001;21:451–472.

    CAS  PubMed  Google Scholar 

  25. Kimber I, Dearman RJ. Allergic contact dermatitis: the cellular effectors. Contact Dermatol 2002;46:1–5.

    Article  Google Scholar 

  26. Finkelman FD, Katona IM, Urban JF, et al. IL-is required to generate and sustain in vivo IgE responses. J Immunol 1988;141:2335–2341.

    CAS  PubMed  Google Scholar 

  27. Kuhn R, Rajewsky K, Muller W. Generation and analysis of interleukin-4-deficient mice. Science 1991;254:707–710.

    Article  CAS  PubMed  Google Scholar 

  28. Romagnani S, Del Prete G, Maggi E, et al. Role of interleukins in induction and regulation of human IgE synthesis. Clin Immunol Immunopathol 1989;50:S13–S23.

    Article  CAS  PubMed  Google Scholar 

  29. Finkelman FD, Katona IM, Mosmann TR, Coffman RL. IFN-γ regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol 1988; 140:1022–1027.

    CAS  PubMed  Google Scholar 

  30. Krishnan L, Mosmann TR. Functional subpopulations of CD4+ T lymphocytes. In: Kimber I, Selgrade MK, eds. T Lymphocyte Subpopulations in Immunotoxicology. Chichester: John Wiley & Sons, 1998, pp. 7–32.

    Google Scholar 

  31. Robinson DS, Hamid Q, Ying S, et al. Predominant Th2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Eng J Med 1992;326:298–304.

    Article  CAS  Google Scholar 

  32. Robinson DS, Hamid Q, Bentley A, Ying S, Kay AB, Durham SR. Activation of CD4+ T cells, increased Th2-type cytokine mRNA expression and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J Allergy Clin Immunol 1993;92:313–324.

    Article  CAS  PubMed  Google Scholar 

  33. Durham SR, Ying S, Varney VA, et al. Cytokine messenger RNA expression for IL-3, IL-, IL-5 and granulocyte/macrophage colony-stimulating factor in the nasal mucosa after local allergen provocation: relationship to tissue eosinophilia. J Immunol 1992; 148:2390–2394.

    CAS  PubMed  Google Scholar 

  34. Topping MD, Venables KM, Luczynska CM, Howe W, Newman Taylor AJ. Specificity of the human IgE response to inhaled acid anhydrides. J Allergy Clin Immunol 1986;77:834–842.

    Article  CAS  PubMed  Google Scholar 

  35. Tarlo S M. Diisocyanate sensitization and antibody production. J Allergy Clin Immunol 1999;103:739–741.

    Article  CAS  PubMed  Google Scholar 

  36. Tee RD, Cullinan P, Welch J, Burge PS, Newman Taylor AJ. Specific IgE to isocyanates: a useful diagnostic role in occupational asthma. J Allergy Clin Immunol 1998;101:709–715.

    Article  CAS  PubMed  Google Scholar 

  37. Bentley AM, Maestrelli P, Saetta M, et al. Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma. J Allergy Clin Immunol 1992;89:821–829.

    Article  CAS  PubMed  Google Scholar 

  38. Del Prete GF, De Carli M, D’Elios MM, et al. Allergen exposure induces the activation of allergen-specific Th2 cells in the airway mucosa of patients with allergic respiratory disorders. Eur J Immunol 1993;23:1445–1449.

    Article  PubMed  Google Scholar 

  39. Zeiss CR, Patterson R, Pruzansky JJ, Miller M, Rosenberg M, Levitz D. Trimellitic anhydride-induced airway syndromes: clinical and immunologic studies. J Allergy Clin Immunol 1977;60:96–103.

    Article  CAS  PubMed  Google Scholar 

  40. Botham PA, Rattray NJ, Woodcock DR, Walsh ST, Hext PM. The induction of respiratory allergy in guinea pigs following intradermal injection of trimellitic anhydride: a comparison with the response to 2,4-dinitrochlorobenzene. Toxicol Lett 1989;47:25–39.

    Article  CAS  PubMed  Google Scholar 

  41. Dearman RJ, Kimber I. Differential stimulation of immune function by respiratory and contact chemical allergens. Immunology 1991;72:563–570.

    CAS  PubMed  Google Scholar 

  42. Dearman RJ, Hegarty JM, Kimber I. Inhalation exposure of mice to trimellitic anhydride induces both IgG and IgE anti-hapten antibody. Int Arch Allergy Appl Immunol 1991;95:70–76.

    Article  CAS  PubMed  Google Scholar 

  43. Dearman RJ, Smith S, Basketter DA, Kimber I. Classification of chemical allergens according to cytokine secretion profiles in murine lymph node cells. J Appl Toxicol 1997; 17:53–62.

    Article  CAS  PubMed  Google Scholar 

  44. Dearman RJ, Kimber I. Cytokine fingerprinting and hazard assessment of chemical respiratory allergy. J Appl Toxicol 2001;21:153–163.

    Article  CAS  PubMed  Google Scholar 

  45. Dearman RJ, Warbrick EV, Skinner R, Kimber I. Cytokine fingerprinting of chemical allergens: species comparisons and statistical analyses. Fd Chem Toxicol 2002;40:107–118.

    Google Scholar 

  46. Dearman RJ, Ramdin LSP, Basketter DA, Kimber I. Inducible interleukin-4-secreting cells provoked in mice during chemical sensitization. Immunology 1994;81:551–557.

    CAS  PubMed  Google Scholar 

  47. Dearman RJ, Betts CJ, Humphreys N, et al. Chemical allergy: considerations for the practical application of cytokine profiling. Toxicol Sci 2003;71:137–145.

    Article  CAS  PubMed  Google Scholar 

  48. Betts CJ, Dearman RJ, Flanagan BF, Kimber I. Temporal changes in cytokine gene expression profiles induced in mice by trimellitic anhydride. Toxicol Lett 2002;136:121–132.

    Article  CAS  PubMed  Google Scholar 

  49. Moussavi A, Dearman RJ, Kimber I, Kemeny DM. Cytokine production by CD4+ and CD8+ T cells in mice following primary exposure to chemical allergens: evidence for functional differentiation of T lymphocytes in vivo. Int Arch Allergy Immunol 1998; 116:116–123.

    Article  CAS  PubMed  Google Scholar 

  50. Dearman RJ, Moussavi A, Kemeny DM, Kimber I. Contribution of CD4+ and CD8+ T lymphocyte subsets to the cytokine secretion patterns induced in mice during sensitization to contact and respiratory chemical allergens. Immunology 1996;89:502–510.

    Article  CAS  PubMed  Google Scholar 

  51. Hayashi M, Higashi K, Kato H, Kaneko H. Assessment of preferential Th1 or Th2 induction by low-molecular-weight compounds using a reverse transcription-polymerase chain reaction method: comparison of two mouse strains, C57BL/6 and BALB/c. Toxicol Appl Pharmacol 2001;177:38–45.

    Article  CAS  PubMed  Google Scholar 

  52. Manetz TC, Pettit DA, Meade BJ. The determination of draining lymph node cell cytokine mRNA levels in BALB/c mice following dermal sodium lauryl sulfate, dinitrofluorobenzene, and toluene diisocyanate exposure. Toxicol Appl Pharmacol 2001;171:174–183.

    Article  CAS  PubMed  Google Scholar 

  53. Vandebriel RJ, De Jong WH, Spiekstra SW, et al. Assessment of preferential T-helper 1 or T-helper 2 induction by low molecular weight compounds using the local lymph node assay in conjunction with RT-PCR and ELIS A for interferon-γ and interleukin-4. Toxicol Appl Pharmacol 2000; 162:77–85.

    Article  CAS  PubMed  Google Scholar 

  54. Van Och FMN, van Loveren H, de Jong WH, Vanderbriel R. Cytokine production induced by low molecular weight chemicals as a function of the stimulation index in a modified local lymph node assay: an approach to discriminate contact sensitizers from respiratory sensitizers. Toxicol Appl Pharmacol 2002; 184:46–56.

    Article  PubMed  Google Scholar 

  55. Farraj AK, Harkema JR, Kaminski NE. Allergic rhinitis induced by intranasal sensitization and challenge with trimellitic anhydride but not with dinitrochlorobenzene or oxazolone in A/J mice. Toxicol Sci 2004;79:315–325.

    Article  CAS  PubMed  Google Scholar 

  56. Ulrich P, Grenet O, Bluemel J, et al. Cytokine expression profiles during murine contact allergy: T helper 2 cytokines are expressed irrespective of the type of contact allergen. Arch Toxicol 2001;75:470–479.

    Article  CAS  PubMed  Google Scholar 

  57. Wang H, Mohapatra SS, HayGlass KT. Evidence for the existence of IL-4 and IFN gamma secreting cells in the T cell repertoire of naive mice. Immunol Lett 1992;31:169–175.

    Article  CAS  PubMed  Google Scholar 

  58. Kimber I. Contact and respiratory sensitization by chemical allergens: uneasy relationships. Am J Contact Dermatol 1995;6:34–39.

    Article  Google Scholar 

  59. Kimber I, Dearman RJ. Chemical respiratory allergy: role of IgE antibody and relevance of route of exposure. Toxicology 2002; 181-182:311–315.

    Article  CAS  PubMed  Google Scholar 

  60. Plitnick LM, Loveless SL, Ladies GS, et al. Cytokine profiling for chemical sensitizers: application of the ribonuclease protection assay and effect of dose. Toxicol Appl Pharmacol 2002; 179:145–154.

    Article  CAS  PubMed  Google Scholar 

  61. Plitnick LM, Loveless SE, Ladies GS, et al. Identifying airway sensitizers: cytokine mRNA profiles induced by various anhydrides. Toxicology 2003;193:191–201.

    Article  CAS  PubMed  Google Scholar 

  62. Warbrick EV, Dearman RJ, Basketter DA, Kimber I. Analysis of interleukin 12 protein production and mRNA expression in mice exposed topically to chemical allergens. Toxicology 1999; 132:57–66.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK

    Rebecca J. Dearman & Ian Kimber

Authors
  1. Rebecca J. Dearman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ian Kimber
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. DyPort Vaccine Company, LLC, Frederick, MD

    Robert V. House

  2. Poison Center and Pharmacovigilance Unit, Lyon Cedex, France

    Jacques Descotes

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Dearman, R.J., Kimber, I. (2007). The Use of Cytokines in the Identification and Characterization of Chemical Allergens. In: House, R.V., Descotes, J. (eds) Cytokines in Human Health. Methods in Pharmacology and Toxicology. Humana Press. https://doi.org/10.1007/978-1-59745-350-9_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-350-9_5

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-467-8

  • Online ISBN: 978-1-59745-350-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation