title: Normal free interleukin-18 (IL-18) plasma levels in dengue virus infection and the need to measure both total IL-18 and IL-18 binding protein levels.
abstract: Activated monocytes/macrophages and T lymphocytes that produce a cytokine storm are assumed to play a pivotal role in the pathogenesis of dengue. Interleukin-18 (IL-18) is a proinflammatory cytokine that is increased during dengue and known to induce gamma interferon (IFN-γ), which is crucial for dengue immune response. No data are available regarding the balance between IL-18 and its natural inhibitor IL-18 binding protein (IL-18BP) and how they interact within the inflammatory reaction of patients with dengue virus infections. Circulating levels of IL-18; IL-18BP; free, biologically active IL-18; the IL-18-dependent proinflammatory cytokine IFN-γ; monocyte-derived cytokines; and ferritin were assessed in adult Indonesian dengue patients (n = 95). Healthy individuals (n = 22) and leptospirosis (n = 19) and enteric fever (n = 6) patients served as controls. Total IL-18 levels were increased during dengue, leptospirosis, and enteric fever compared to healthy controls. However, due to a concurrent increase in IL-18BP levels, biologically active IL-18 levels remained similar in the different phases of dengue and in patients with leptospirosis. Biologically active IL-18 levels were also similar in patients with severe and nonsevere dengue. In conclusion, high total IL-18 and IL-18BP levels concur in dengue virus infections, leptospirosis, and enteric fever. This resulted in unchanged levels of free, biologically active IL-18 in dengue and leptospirosis, which underlines the importance of measuring both IL-18 and IL-18BP when studying the role of IL-18 in diseases.
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Meta.Michels@radboudumc.nl.
authors: Meta
authors: M
authors: Michels
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Quirijn
authors: Q
authors: de Mast
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Mihai G
authors: MG
authors: Netea
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Leo A
authors: LA
authors: Joosten
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Charles A
authors: CA
authors: Dinarello
authors: Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia.
authors: Pandji I F
authors: PI
authors: Rudiman
authors: Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia.
authors: Sylvia
authors: S
authors: Sinarta
authors: Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia.
authors: Rudi
authors: R
authors: Wisaksana
authors: Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia.
authors: Bachti
authors: B
authors: Alisjahbana
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: André J A M
authors: AJ
authors: van der Ven
mesh_terms: D000293:Adolescent; D000328:Adult; D003715:Dengue / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D007214:Indonesia; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D020382:Interleukin-18 / Q000097:blood*; D007922:Leptospirosis / Q000276:immunology / Q000473:pathology; D008297:Male; D010949:Plasma / Q000737:chemistry*; D011446:Prospective Studies; D014435:Typhoid Fever / Q000276:immunology / Q000473:pathology; D055815:Young Adult
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C118370:interleukin-18 binding protein