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

Abstract

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.

Methods for the identification of chemical respiratory allergens in rodents: comparisons of cytokine profiling with induced changes in serum IgE

“…The cytokine secretion profiles provoked by different classes of chemical allergen are selective, not absolute. Expression of type 2 cytokines has also been detected by other investigators after treatment with contact allergens such as DNCB, albeit at much lower levels than those stimulated by TMA (Dearman et al, , 2002aHayashi et al, 2001). The important point is that, under conditions where DNCB and TMA are both of equivalent immunogenicity, preferential, but not exclusive, type 1 and type 2 cytokine expression phenotypes are observed (Vandebriel et al, 2000;Hayashi et al, 2001;Manetz et al, 2001;Dearman et al, 2002a;Plitnick et al, 2002).…”

“…Expression of type 2 cytokines has also been detected by other investigators after treatment with contact allergens such as DNCB, albeit at much lower levels than those stimulated by TMA (Dearman et al, , 2002aHayashi et al, 2001). The important point is that, under conditions where DNCB and TMA are both of equivalent immunogenicity, preferential, but not exclusive, type 1 and type 2 cytokine expression phenotypes are observed (Vandebriel et al, 2000;Hayashi et al, 2001;Manetz et al, 2001;Dearman et al, 2002a;Plitnick et al, 2002). It is not possible in the experiments conducted by Ulrich and colleagues to compare directly the ability of DNCB and TMA to provoke selective type 1 and type 2 cytokine secretion patterns because the concentration of DNCB used was considerably less immunogenic than was the dose of TMA selected.…”

Comparative Studies of Lymph Node Cell Subpopulations and Cytokine Expression in Murine Model for Testing the Potentials of Chemicals to Induce Respiratory Sensitization

“…Since it has been suggested frequently that respiratory sensitizers cause Th2 type responses, while dermal sensitizers produce Th1 type response, the estimation of the levels of cytokines, mainly IL-4 and IFN-γ, is considered to be an indication of chemical's potential to cause sensitization. This approach has been used for several years and studied in different animal models, using different chemical compounds and different techniques [8,[26][27][28][29]41]. to induce allergies.…”

Investigation of the chemical-induced selective type II (TH2) allergic response in mice: Effect of the length of the sensitizing phase

“…For example, a selective type II (T H 2) allergic response such as respiratory hypersensitivity can be induced in susceptible persons after airway exposure to a chemical allergen. A variety of chemicals (including various diisocyanates, acid anhydrides, and reactive dyes) can cause allergic sensitization of the respiratory tract associated with occupational asthma and other symptoms Dearman., 1997, 2002;Dearman et al, 2002;Arts et al, 2003;Pauluhn et al, 2003;.…”