Differential requirements for interleukin (IL)-4 and IL-13 in protein contact dermatitis induced by Anisakis.
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-4Ralpha 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-4Ralpha 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 T(H)2 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-4Ralpha or with impaired IL-4Ralpha 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.
Nieuwenhuizen
N
N
IIDMM, University of Cape Town, South Africa.
Herbert
D R
DR
Brombacher
F
F
Lopata
A L
AL
D000485:Allergens / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology / Q000378:metabolism; D000818:Animals; D017163:Anisakis / Q000276:immunology*; D000913:Antibodies, Protozoan / Q000097:blood; D000947:Antigens, Helminth / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology / Q000469:parasitology* / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology
D000485:Allergens; D000913:Antibodies, Protozoan; D000947:Antigens, Helminth; D007074:Immunoglobulin G; D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin