Nieuwenhuizen, N., Herbert, D.R., Brombacher, F., and Lopata, A.L. (2009) Differential requirements for interleukin (IL)-4 and IL-13 in protein contact dermatitis induced by Anisakis. Allergy, 64 (9). pp. 1309-1318.

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Abstract

Background:  Exposure to antigens of the fish parasite Anisakis is associated with the development of protein contact dermatitis in seafood-processing workers. Understanding the basic mechanisms controlling allergic sensitization through the skin is critical for designing therapies that will prevent the progression of allergic disease.

Objective:  To investigate the roles of interleukin (IL)-4, IL-13 and the IL-4Rα in both local skin pathology and systemic sensitization following epicutaneous exposure to Anisakis proteins.

Methods:  BALB/c wild-type (WT) mice and mice deficient in IL-4, IL-13 or IL-4 and IL-13, as well as mice with cell-specific impairment of IL-4Rα expression, were sensitized to Anisakis antigen by repeated epicutaneous application of Anisakis extract. Following this sensitization, skin pathology was recorded and systemic responses were investigated. Intravenous challenge with Anisakis extract was performed to test for the development of biologically relevant systemic sensitization.

Results:  In WT mice, epicutaneous sensitization with Anisakis larval antigens induced localized inflammation, epidermal hyperplasia, production of TH2 cytokines, antigen-specific IgE and IgG1. Intravenous challenge of sensitized mice resulted in anaphylactic shock. Interestingly, IL-13 deficient mice failed to develop epidermal hyperplasia and inflammation, whilst anaphylaxis was reduced only in strains deficient either in IL-4 only, or deficient in IL-4 and IL-13 concurrently, as well as in mice deficient in IL-4Rα or with impaired IL-4Rα expression on CD4+ T cells.

Conclusions:  Interleukin-13 plays a central role in protein contact dermatitis associated with repeated epicutaneous exposure to Anisakis extract, whereas IL-4 drives systemic sensitization and resultant anaphylactic shock.

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