title: IL-18 binding protein protects against contact hypersensitivity.
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.
authors.affiliation: Department of Immunology, Serono Pharmaceutical Research Institute, Geneva, Switzerland. Thomas.Plitz@serono.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Plitz
authors.forename: Pierre
authors.initials: P
authors.lastname: Saint-Mézard
authors.forename: Masataka
authors.initials: M
authors.lastname: Satho
authors.forename: Susanne
authors.initials: S
authors.lastname: Herren
authors.forename: Caroline
authors.initials: C
authors.lastname: Waltzinger
authors.forename: Marcelo
authors.initials: M
authors.lastname: de Carvalho Bittencourt
authors.forename: Marie H
authors.initials: MH
authors.lastname: Kosco-Vilbois
authors.forename: Yolande
authors.initials: Y
authors.lastname: Chvatchko
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002199:Capillary Permeability / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004139:Dinitrofluorobenzene / Q000008:administration & dosage; D015536:Down-Regulation / Q000276:immunology; D004431:Ear, External / Q000276:immunology / Q000473:pathology; D006023:Glycoproteins / Q000008:administration & dosage / Q000627:therapeutic use*; D006241:Haptens / Q000008:administration & dosage; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016207:Cytokines; D006023:Glycoproteins; D006241:Haptens; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; C118370:interleukin-18 binding protein; D004139:Dinitrofluorobenzene