Characterization of chemical allergens as a function of divergent cytokine secretion profiles induced in mice.
Allergic contact dermatitis (contact sensitivity) may be caused by a wide variety of chemicals. In addition, some chemical allergens may also induce respiratory sensitization. It has been demonstrated previously that topical exposure of mice to chemical contact and respiratory sensitizers stimulates divergent immune responses consistent with the selective activation of T helper 1 (Th1)- and Th2-type cells, respectively. Thus, exposure to trimellitic: anhydride (TMA) induces hapten-specific IgE antibody and a substantial increase in the total serum concentration of IgE. Conversely, oxazolone fails to provoke IgE production. In addition, lymph node cells (LNC) isolated following repeated topical exposure of mice to oxazolone or TMA display cytokine secretion profiles characteristic of Th1- and Th2-type cell stimulation. The purpose of the present investigations was to determine whether chemical allergens other than TMA and oxazolone, the respiratory allergen toluene diisocyanate (TDI) and the skin sensitizer dinitrofluorobenzene (DNFB), provoke differential cytokine expression. The production of the Th1-type product interferon gamma (IFN-gamma) and the Th2-type cytokines interleukins 4 and 10 (IL-4 and IL-10) by TDI- and DNFB-activated LNC has been measured. LNC derived from DNFB-exposed animals expressed substantial amounts of IFN-gamma, but only low levels of IL-10 and mitogen-inducible IL-4; exposure to TDI resulted in the converse profile of cytokine secretion. These data demonstrate that repeated topical administration of chemical allergen of different classes elicits in mice divergent cytokine secretion patterns consistent with the selective stimulation of distinct Th subsets. Analysis of such cytokine production profiles may permit in a single integrated assay the simultaneous identification and classification of chemical allergens.
Dearman
R J
RJ
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom.
Basketter
D A
DA
Kimber
I
I
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000209:etiology; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000494:pharmacology; D010796:Phthalic Anhydrides / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D014051:Toluene 2,4-Diisocyanate / Q000494:pharmacology
D000485:Allergens; D016207:Cytokines; D010796:Phthalic Anhydrides; D016753:Interleukin-10; D010081:Oxazolone; D014051:Toluene 2,4-Diisocyanate; C015559:trimellitic anhydride; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene