IL-18 binding protein protects against contact hypersensitivity.
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.
Plitz
Thomas
T
Department of Immunology, Serono Pharmaceutical Research Institute, Geneva, Switzerland. Thomas.Plitz@serono.com
Saint-Mézard
Pierre
P
Satho
Masataka
M
Herren
Susanne
S
Waltzinger
Caroline
C
de Carvalho Bittencourt
Marcelo
M
Kosco-Vilbois
Marie H
MH
Chvatchko
Yolande
Y
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
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