Interleukins 5 and 13 characterize immune responses to respiratory sensitizing acid anhydrides

J Appl Toxicol. 2002 Sep-Oct;22(5):317-25. doi: 10.1002/jat.865.


There is some debate regarding whether occupational asthma induced by respiratory sensitizing acid anhydrides is mediated by the induction of T helper (Th) 2-type responses and the production of IgE, with failure to detect specific IgE antibody in some symptomatic patients. In the current investigations, cytokine secretion profiles induced in draining lymph node cells (LNC) by topical application to BALB/c strain mice of trimellitic anhydride (TMA), phthalic anhydride (PA) and maleic anhydride (MA) have been examined. Responses were compared with those induced by exposure to 2,4-dinitrochlorobenzene (DNCB), a contact allergen that lacks respiratory sensitizing potential. Exposure to all three acid anhydrides stimulated vigorous expression of interleukin (IL)-5, IL-10 and IL-13 but relatively low levels of the type 1 cytokines interferon-gamma (IFN-gamma) and IL-12. In addition, TMA-activated LNC expressed high levels of mitogen-inducible IL-4 whereas MA and PA displayed a lesser potential to elaborate this cytokine. The DNCB-stimulated LNC exhibited the converse type 1 phenotype of cytokine expression. The CD4(+) Th2 cells were the primary source of type 2 cytokines. Respiratory sensitizing acid anhydrides induce a predominantly Th2 cytokine phenotype, including the expression of IL-5 and IL-13, cytokines which in the presence of only very low levels of IL-4 may provide for an IgE-independent mechanism for the development of chemical respiratory allergy. These data provide additional support for the use of cytokine secretion profiling for the prospective identification of chemical respiratory allergens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Allergens / toxicity
  • Anhydrides / immunology*
  • Anhydrides / toxicity
  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Dinitrochlorobenzene / immunology
  • Dinitrochlorobenzene / toxicity
  • Female
  • Interleukin-13 / biosynthesis
  • Interleukin-13 / metabolism*
  • Interleukin-5 / biosynthesis
  • Interleukin-5 / metabolism*
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism*
  • Maleic Anhydrides / immunology
  • Maleic Anhydrides / toxicity
  • Mice
  • Mice, Inbred BALB C
  • Mitogens / immunology
  • Mitogens / toxicity
  • Phthalic Anhydrides / immunology
  • Phthalic Anhydrides / toxicity
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / metabolism


  • Allergens
  • Anhydrides
  • Dinitrochlorobenzene
  • Interleukin-13
  • Interleukin-5
  • Maleic Anhydrides
  • Mitogens
  • Phthalic Anhydrides
  • trimellitic anhydride
  • phthalic anhydride