title: Expression of Interleukin-1 and Interleukin-1 Receptors Type 1 and Type 2 in Hodgkin Lymphoma.
abstract: Signaling through the IL-1-receptor type 1 (IL-1R1), IL-1 is required for initiation and maintenance of diverse activities of the immune system. A second receptor, IL-1R2, blocks IL-1 signal transduction. We studied expression of IL-1beta, IL-1R1, and IL-1R2 in 17 Hodgkin lymphomas (HL) by in situ hybridization (ISH). IL-1beta expressing cells, morphologically consistent with endothelial cells and fibroblasts, occurred in all HL tissues with elevated transcript levels in areas of active fibrosis. Hodgkin and Reed-Sternberg (HRS) cells of all cases expressed low IL-1R1 transcript levels in some tumor cells, and high levels of IL-1R2 in large proportions of HRS cells. Only few bystander cells showed low levels of IL-1R1 and IL-1R2 RNA. Supernatants of 4 out of 7 HL-derived cell lines contained soluble IL-1R2 protein at high levels. HL patient sera carried variably amounts of IL-1R2 protein with significantly increased titers in patients with active disease compared to patients in complete remission and control individuals without HL. Western blots and co-immunoprecipitations showed binding of the IL-1R2 to the intracellular IL-1R-accessory protein (IL-1IRAcP). These data suggest functions of the IL-1R2 as a "decoy-receptor" sequestrating paracrine IL-1 extracellularly and intracellularly by engaging IL-1IRAcP, thus depriving IL1-R1 molecules of their extracellular and intracellular ligands. Expression of IL1-R2 by HRS cells seems to contribute to local and systemic modulation of immune function in HL.
authors.affiliation: Department of Medicine A-Hematology/Oncology, University Hospital Muenster, Muenster, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Oelmann
authors.affiliation: Pathodiagnostik Berlin, Berlin, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.affiliation: Department of Medicine A-Hematology/Oncology, University Hospital Muenster, Muenster, Germany.
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Institute of Pathology, Vivantes Hospitals, Berlin, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Herbst
mesh_terms: D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D053574:Receptors, Interleukin-1 Type II / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D053583:Interleukin-1beta; D012333:RNA, Messenger; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II