Abstract
Allergic contact dermatitis, the clinical manifestation of contact hypersensitivity, is one of the most common disorders of the skin. It is elicited upon multiple cutaneous re-exposure of sensitized individuals to the sensitizing agent. In this study, we demonstrate that using IL-18 binding protein (IL-18BP) to neutralize IL-18 significantly reduced clinical symptoms in a murine model of contact hypersensitivity. Furthermore, IL-18BP alleviated the relapses during established disease, as indicated by significant protection during re-exposure of mice that had previously undergone a contact hypersensitivity response without treatment. Although edema was not influenced, IL-18BP reduced the number of T cells homing to sites of inflammation, resulting in diminished local production of IFN-gamma. Thus, by preventing the accumulation of effector T cells to the target tissue, IL-18BP appears to be a potent protective mediator to counter skin inflammation during contact hypersensitivity. Taken together with the evidence that IL-18 is present in tissue samples of the human disease, our data reinforces IL-18BP as a candidate for this therapeutic indication.
MeSH terms
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Administration, Cutaneous
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Animals
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Capillary Permeability / immunology
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Cell Movement / immunology
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Cells, Cultured
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Cytokines / antagonists & inhibitors
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Cytokines / metabolism
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Dermatitis, Contact / immunology*
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Dermatitis, Contact / pathology
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Dermatitis, Contact / physiopathology
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Dermatitis, Contact / prevention & control*
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Dinitrofluorobenzene / administration & dosage
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Down-Regulation / immunology
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Ear, External / immunology
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Ear, External / pathology
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Glycoproteins / administration & dosage
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Glycoproteins / therapeutic use*
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Haptens / administration & dosage
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Humans
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Inflammation Mediators / administration & dosage
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Inflammation Mediators / therapeutic use
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Intercellular Signaling Peptides and Proteins
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Interleukin-18 / antagonists & inhibitors
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Interleukin-18 / biosynthesis
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Interleukin-18 / metabolism*
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Lymphocyte Count
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Mice
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Mice, Inbred C57BL
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / pathology
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Cytokines
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Glycoproteins
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Haptens
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Inflammation Mediators
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Intercellular Signaling Peptides and Proteins
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Interleukin-18
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Receptors, Antigen, T-Cell, alpha-beta
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Tumor Necrosis Factor-alpha
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interleukin-18 binding protein
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Dinitrofluorobenzene