Classification of chemical allergens according to cytokine secretion profiles of murine lymph node cells.
Characteristic cytokine secretion profiles, consistent with the selective activation of discrete functional subpopulations of T helper (Th) cells, have been demonstrated following repeated topical exposure of mice to chemical contact or respiratory allergens. Draining lymph node cells (LNC) derived from animals treated with the respiratory allergen trimellitic anhydride (TMA; 10%) expressed high levels of the Th2 cytokines interleukins 4 and 10, but little of the Th1 cell product interferon gamma. Under conditions of exposure of equivalent immunogenicity with respect to LNC proliferation, the contact allergen 2,4-dinitrochlorobenzene (DNCB) provoked the converse pattern of cytokine secretion. The purpose of the present investigations was to examine dose-response relationships with respect to cytokine production with a wider range of chemical allergens. In each case, cytokine secretion patterns were compared with those observed with LNC prepared from animals exposed concurrently to TMA or DNCB. Despite some inter-experimental variation in the absolute amounts of cytokines produced, DNCB- and TMA-activated LNC invariably expressed Th1- and Th2-type patterns, respectively. At all concentrations tested, the contact allergens isoeugenol and formaldehyde stimulated a Th1-type cytokine secretion profile, whereas a Th2-type pattern was induced following exposure to the chemical respiratory allergens cyanuric chloride and diphenylmethane diisocyanate. These data demonstrate that divergent cytokine secretion profiles characterize immune responses to different classes of chemical allergen and suggest that it may be possible, in a single integrated assay, to identify and classify chemical allergens as a function of induced cytokine production patterns.
Dearman
R J
RJ
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Smith
S
S
Basketter
D A
DA
Kimber
I
I
D000485:Allergens / Q000145:classification* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype
D000485:Allergens; D016207:Cytokines; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma