Cytokine expression profiles during murine contact allergy: T helper 2 cytokines are expressed irrespective of the type of contact allergen.
We have investigated the cytokine response pattern following sensitisation (induction) of BALB/c mice with different chemicals (dinitrochlorobenzene, dinitrofluorobenzene, oxazolone, glutaraldehyde, formaldehyde, trimellitic anhydride, croton oil) and elicitation (challenge) of contact allergy in sensitised animals. The results of our investigations showed that different chemicals induced both T helper (Th) 1 cytokines [interleukin (IL) 2, interferon beta (IFNgamma) [corrected] and Th2 cytokines (IL-4, IL-10) at different stages during murine contact allergy. We also confirmed our previous findings that IL-4 and IL-10 release were up-regulated during the challenge phase regardless the contact allergen used, whereas the release of IFNgamma [corrected] did not show a clear preference for being up- or down-regulated. In our hands, the increased expression of Th2 cytokines after challenge exposure to contact allergens appeared as a stable marker of secondary contact allergenic responses. Quantitative differences in the expression of IL-4 were observed between different contact allergens. The present results clearly indicate that skin sensitisers were able to elicit cytokine response patterns, which could not be related to a clear-cut Th1 or Th2 type of cytokine response. Furthermore, dermal application of contact allergens produced different kinetics of cytokine secretion upon induction and challenge. In our hands, the co-expression of Th1 and Th2 type cytokines appeared as a universal consequence of dermal application of contact allergens to responsive mice. Our results indicate that co-expression of Th1 and Th2 cytokines during contact allergy is an important feature of murine contact allergy in responsive mice and that chemicals differ in their potency to induce the expression of these cytokines. Furthermore, the results do not support the view that different chemicals induce Th1 or Th2 cytokines in a mutually exclusive manner depending on their preference for inducing either contact or respiratory allergy. The results are expected to renew the discussion about the usefulness of the Th1/Th2 paradigm in certain areas of immunotoxicology.
Ulrich
P
P
PCS-Genetic and Experimental Toxicology, Novartis Pharma AG, Basel, Switzerland. peter.ulrich@pharma.novartis.com
Grenet
O
O
Bluemel
J
J
Vohr
H W
HW
Wiemann
C
C
Grundler
O
O
Suter
W
W
D000485:Allergens / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004431:Ear, External / Q000187:drug effects / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
D000485:Allergens; D016207:Cytokines