title: Neutrophil extracellular traps regulate IL-1β-mediated inflammation in familial Mediterranean fever.
abstract: OBJECTIVE
  Inflammatory attacks of familial Mediterranean fever (FMF) are characterised by circulation and influx of high number of polymorphonuclear neutrophils (PMN) in the affected sites and profound therapeutic effect of IL-1β inhibitors. We investigated the role of neutrophil extracellular traps (NET) in the pathogenesis of FMF, and their involvement in IL-1β production.
  
  
  METHODS
  Blood samples were obtained from six FMF patients during remissions and from three patients during attacks. NET formation and NET components were studied by fluorescence techniques, immunobloting and MPO-DNA complex ELISA.
  
  
  RESULTS
  PMNs from patients released NETs decorated with IL-1β during disease attacks. On the other hand, PMNs from patients during remission were resistant to inflammatory stimuli that induce NET release in PMNs from control subjects. Lower basal autophagy levels were identified in PMNs during remission, while induction of autophagy facilitated NET release, suggesting that autophagy is involved in the regulation of NET release. During the resolution of attacks, inhibition of NET formation by negative feedback mechanism was also observed. The anti-inflammatory agents, colchicine and DNAse I, inhibited IL-1β production in PMNs and IL-1β activity in NETs, respectively.
  
  
  CONCLUSIONS
  We suggest two additive events for triggering the FMF attack; the production of IL-1β by PMNs and its release through NETs. At the same time NETs, homeostatically, downregulate further NETosis, facilitating the resolution of attack. Compensatorly, lower basal autophagy of PMNs may protect from crises by attenuating the release of pro-inflammatory NETs.
authors.affiliation: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece First Department of Internal Medicine, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors.forename: Eirini
authors.initials: E
authors.lastname: Apostolidou
authors.affiliation: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece First Department of Internal Medicine, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Skendros
authors.affiliation: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kambas
authors.affiliation: Department of Clinical Pathobiochemistry, Technical University Dresden, Dresden, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mitroulis
authors.affiliation: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Theocharis
authors.initials: T
authors.lastname: Konstantinidis
authors.affiliation: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Akrivi
authors.initials: A
authors.lastname: Chrysanthopoulou
authors.affiliation: Laboratory of Cellular and Molecular Biology, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Nakos
authors.affiliation: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Victoria
authors.initials: V
authors.lastname: Tsironidou
authors.affiliation: Laboratory of Cellular and Molecular Biology, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Koffa
authors.affiliation: Fourth Department of Internal Medicine, National University of Athens Medical School, Athens, Greece Biomedical Research Foundation of Academy of Athens, Centre of Immunology and Transplantations, Athens, Greece.
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Boumpas
authors.affiliation: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece First Department of Internal Medicine, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Ritis
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001343:Autophagy / Q000276:immunology; D016022:Case-Control Studies; D003078:Colchicine / Q000494:pharmacology; D003850:Deoxyribonuclease I / Q000494:pharmacology; D065206:Extracellular Traps / Q000187:drug effects / Q000276:immunology*; D010505:Familial Mediterranean Fever / Q000276:immunology*; D025461:Feedback, Physiological; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D012074:Remission Induction; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D003850:Deoxyribonuclease I; D003078:Colchicine
keywords: Cytokines; Familial Mediterranean Fever; Inflammation