title: Cytokine fingerprinting of chemical allergens: species comparisons and statistical analyses.
abstract: The cellular and molecular mechanisms that result in the induction of chemical respiratory sensitization are unclear, although there is evidence for the development of T helper (Th) 2 type responses and, in some cases, the production of IgE. We have compared cytokine secretion patterns stimulated by topical exposure of BALB/c strain mice or Brown Norway (BN) strain rats to the reference respiratory allergen trimellitic anhydride (TMA), or to the reference contact allergen 2,4-dinitrochlorobenzene (DNCB). Under conditions where TMA and DNCB provoke similar levels of immune activation [increases in lymph node cell (LNC) cellularity and proliferation] divergent cytokine expression patterns are elicited. TMA-activated LNC isolated from BALB/c mice or BN rats elaborated high levels of the Th2-type cytokines interleukin (IL)-10 and IL-13, but relatively little of the Th1-type cytokines IL-12 or interferon gamma. For LNC derived from both species there was a requirement for restimulation in vitro with the mitogen concanavalin A for IL-4 production. Generally, DNCB-stimulated LNC displayed the converse type 1 cytokine phenotype. The cytokine secretion profiles of LNC isolated from BN rats were considerably more variable than those observed for LNC from BALB/c mice. Statistically significant differences (P<0.01) between DNCB- and TMA-activated LNC were recorded for all cytokines in BALB/c strain mice. For the BN rat, differences reached statistical significance (P<0.01) only for the expression of IL-4 and IL-13. These data demonstrate that the intrinsic ability of DNCB and TMA to promote preferential Th1- and Th2-type responses, respectively, is species-independent and provide further evidence that chemical respiratory allergens are associated with polarized Th2-type responses. For the prospective assessment of chemical respiratory allergens as a function of induced cytokine secretion profiles, however, these data suggest that the use of the BALB/c strain mouse will provide the more robust method.
authors.affiliation: Syngenta Central Toxicology Laboratory, Alderley ParkMacclesfield, Cheshire SK10 4TJ, UK. rebecca.dearman@syngenta.com
authors.forename: R J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: E V
authors.initials: EV
authors.lastname: Warbrick
authors.forename: R
authors.initials: R
authors.lastname: Skinner
authors.forename: I
authors.initials: I
authors.lastname: Kimber
mesh_terms: D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology; D004137:Dinitrochlorobenzene / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007509:Irritants / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011914:Rats, Inbred BN; D012140:Respiratory Tract Diseases / Q000209:etiology / Q000276:immunology; D013045:Species Specificity; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D004137:Dinitrochlorobenzene; D007509:Irritants; D010796:Phthalic Anhydrides; D007073:Immunoglobulin E; C015559:trimellitic anhydride