Induction of allergic inflammation by interleukin-18 in experimental animal models.
Interleukin-18 (IL-18) has been regarded as a proinflammatory cytokine because of its potent interferon-gamma-inducing activity. However, mutant mice that release excess amounts of IL-18 spontaneously develop pruritic chronic dermatitis-like atopic dermatitis (AD), suggesting the importance of IL-18 for the development of AD. Intriguingly, depletion of il-18 but not stat6, an essential transcriptional factor for IL-4 signaling, rescues the mice from AD, indicating IL-18-dependent, T-helper 2 (Th2) cell-independent AD. This type of AD is classified as innate-type allergy in contrast to Th2 cell-dependent ordinary allergy. Consistent with the previous studies, mice transferred with antigen-specific Th1 cells exhibit no airway hyperresponsiveness and respiratory eosinophilic inflammation after challenge with antigen alone. However, they suffer from asthma upon challenge with antigen plus IL-18, with comparable levels of both the alterations as in those transferred with Th2 cells following challenge with antigen. The former type of asthma is categorized as Th1-associated allergy. Therefore, it is definitely necessary to evaluate whether individual allergic disorders involve either of these IL-18-mediated pathways or a Th2-mediated one.
Tsutsui
Hiroko
H
Department of Immunology & Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan.
Yoshimoto
Tomohiro
T
Hayashi
Nobuki
N
Mizutani
Hitoshi
H
Nakanishi
Kenji
K
D000818:Animals; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism*; D020382:Interleukin-18 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D051193:Toll-Like Receptors
D020382:Interleukin-18; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors