Cytokine profiling of chemical allergens in mice: Impact of mitogen on selectivity of response

Rebecca Jane Dearman, Catherine Jean Betts, Helen Theresa Caddick, Ian Kimber

    Research output: Contribution to journalArticlepeer-review

    Abstract

    A major constraint in the development of methods for the identification of chemical respiratory allergens is the continuing uncertainty regarding the mechanisms of this disease and in particular the role of IgE antibody. There is, however, increasing evidence that respiratory sensitization is favoured by the induction of a selective type 2 cytokine response. The current investigations focus on the potential application of cytokine profiling to the identification of chemical respiratory sensitizers. The objective is to determine the optimal configuration of the method for discrimination between chemical contact and respiratory sensitizers. The reference contact sensitizer 2,4- dinitrochlorobenzene (DNCB) and reference respiratory sensitizer trimellitic anhydride (TMA), which have been shown to induce type 1 and type 2 cytokine profiles, respectively, were utilized. Variables investigated included cell concentration, time in culture, dosing regimens (a 13 day and a truncated 8 day protocol) and the impact of restimulation in vitro with T cell mitogens. Cell culture conditions were critical for the selectivity of the response, with the addition of mitogen resulting in a less discriminatory pattern of cytokine expression, particularly for the type 1 cytokine interferon γ (IFN-γ). Furthermore, a 13 day exposure period was required for vigorous expression of IFN- by DNCB-activated cells, whereas type 2 cytokine expression by TMA-stimulated cells was recorded after 8 days. These data demonstrate that the most optimal method for cytokine profiling is a chronic (13 day) exposure regime followed by culture of lymph node cells at 107 cells ml 1 for120 h in the absence of mitogen. Copyright ©2008 John Wiley & Sons, Ltd.
    Original languageEnglish
    Pages (from-to)233-241
    Number of pages8
    JournalJournal of Applied Toxicology
    Volume29
    Issue number3
    DOIs
    Publication statusPublished - Apr 2009

    Keywords

    • 2,4-dinitrochlorobenzene
    • Chemical allergens
    • Cytokines
    • Mitogen
    • Trimellitic anhydride

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