title: IL-18 is highly expressed in inflammatory infiltrates of submandibular glands in patients with immunoglobulin G4-related disease.
abstract: Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a new disease entity characterized by high serum IgG4 concentrations, infiltration of IgG4-positive plasmacytes, and fibrosis of various organs. Several groups have reported that IgG4-RD is a unique inflammatory disorder characterized by an immune reaction predominantly mediated by T helper (Th) 2 and regulatory T cells. Meanwhile, recent studies have demonstrated that interleukin (IL) 18 has a potential to trigger the production of Th2 cytokines by Th1 cells. We analyzed IL-18 expression in submandibular glands of patients with IgG4-RD (20 cases) and controls (19 cases) by immunohistochemical analysis and quantitative real-time reverse-transcription polymerase chain reaction. We found that IL-18 was highly expressed in submandibular glands of patients with IgG4-RD than in controls with both protein (P < .05, χ(2) test) and messenger RNA levels (P < .05, Mann-Whitney U test). In addition, the expression of IL-18 and IL-13 was correlated in submandibular glands of patients with IgG4-RD. Moreover, by analyzing dual immunofluorescence staining, a few numbers of cells were double positive for IL-13 and interferon γ at the inflammatory infiltrates of submandibular glands of patients with IgG4-RD. These data suggest a possibility that IL-13 is produced by Th1 cells. We speculated that IL-18 stimulates Th1 cells producing Th2 cytokines and enhances the immune reaction of Th2 cytokines in pathogenesis of IgG4-RD.
authors.affiliation: Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Komori
authors.affiliation: Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Wakisaka
authors.affiliation: Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Nakanishi-Yagi
authors.affiliation: Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Endo
authors.affiliation: Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Murono
authors.affiliation: Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan. Electronic address: tomoy@med.kanazawa-u.ac.jp.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013363:Submandibular Gland / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: C000589760:IL18 protein, human; D007074:Immunoglobulin G; D020382:Interleukin-18
keywords: IFN-γ; IL-13; IL-18; IgG4-RD; Salivary glands