title: Interferon-beta and adhesion molecules (E-selectin and s-intracellular adhesion molecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling.
abstract: Retinal vasculitis is a major component of ocular inflammation that plays a role in retinal tissue damage in patients with idiopathic uveitis and Behçet's disease. Here we show that type 1 interferons (IFN alpha/beta) were not detected in sera from normal individuals but were identified in up to 46% of the sera from retinal vasculitis patients. The predominant form of IFN observed was IFN-beta, which was detected in 39% of Behçet's disease patients and 47% of idiopathic uveitis patients. Seven patients whose sera contained IFN-beta were monitored prospectively. IFN-beta was shown to be present for 6-12 months in all seven of the sera samples tested. Furthermore, the adhesion molecule profile identified in this study was strikingly different when Behçet's and uveitis patient sera were compared to sera from normal controls. Sera from Behçet's disease patients contained significantly elevated levels of the soluble adhesion molecules, sE-selectin and s-intracellular adhesion molecule-1 (sICAM-1), whereas sera from patients with idiopathic uveitis contained significantly increased sE-selectin. In vitro studies evaluating the cell source of these cytokines revealed that polyriboinosinic polyribocytidylic acid (poly I:C) activated retinal vascular endothelial cells produce sE-selectin, sICAM-1 and IFN-beta. Production of these molecules was inhibited by pretreatment with anti-Toll-like receptor 3 (TLR-3) antibody. In conclusion, IFN-beta, sE-selectin and sICAM-1 are elevated in patients with retinal vasculitis and are induced in retinal vascular endothelial cells in vitro by activating the innate immune system through TLR-3. Further analysis of innate immune signalling may prove to be a novel target for future studies on pathogenic mechanisms and therapeutic approaches in retinal vasculitis.
authors.affiliation: Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Lee
authors.forename: L C
authors.initials: LC
authors.lastname: Hooper
authors.forename: L
authors.initials: L
authors.lastname: Kump
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: R
authors.initials: R
authors.lastname: Nussenblatt
authors.forename: J J
authors.initials: JJ
authors.lastname: Hooks
authors.forename: B
authors.initials: B
authors.lastname: Detrick
mesh_terms: D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001528:Behcet Syndrome / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D019040:E-Selectin / Q000097:blood* / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood* / Q000378:metabolism; D007369:Interferon Inducers / Q000494:pharmacology; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology; D016899:Interferon-beta / Q000097:blood* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000378:metabolism; D031300:Retinal Vasculitis / Q000097:blood* / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014605:Uveitis / Q000097:blood / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D019040:E-Selectin; D007369:Interferon Inducers; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D012330:RNA, Double-Stranded; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016899:Interferon-beta; D007371:Interferon-gamma; D011070:Poly I-C