title: Deficient production of IL-1 receptor antagonist and IL-6 coupled to oxidative stress in cryopyrin-associated periodic syndrome monocytes.
abstract: OBJECTIVE
  To determine whether dysregulated production of cytokines downstream of interleukin (IL)-1 participates in the pathophysiology of cryopyrin-associated periodic syndromes (CAPS).
  
  
  METHODS
  Primary monocytes from patients with CAPS, unstimulated or after stimulation with lipopolysaccharide (LPS) and other Toll-like receptor (TLR) agonists, were examined for signs of stress and production of IL-1β, IL-1 receptor antagonist (IL-1Ra) and IL-6 in comparison with monocytes from patients with autoimmune diseases and from healthy donors.
  
  
  RESULTS
  Unstimulated CAPS monocytes showed mild signs of stress including elevated levels of reactive oxygen species and fragmented mitochondria. Stress signs were worsened by TLR stimulation and eventually led to protein synthesis inhibition with strong impairment of production of cytokines downstream of IL-1, such as IL-1Ra and IL-6. These defects were not detected in monocytes from autoimmune patients and healthy donors.
  
  
  CONCLUSIONS
  The stress state of LPS-stimulated CAPS monocytes and the consequent inhibition of translation are likely to be responsible for the impaired production of IL-1Ra and IL-6. The deficient secretion of these cytokines coupled with increased IL-1β release explains the severity of the IL-1-related clinical manifestations and the predominant implication of innate immunity in CAPS.
authors: Cell Biology Unit, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, Genova 16132, Italy.
authors: Sonia
authors: S
authors: Carta
authors: Sara
authors: S
authors: Tassi
authors: Laura
authors: L
authors: Delfino
authors: Alessia
authors: A
authors: Omenetti
authors: Salvatore
authors: S
authors: Raffa
authors: Maria Rosaria
authors: MR
authors: Torrisi
authors: Alberto
authors: A
authors: Martini
authors: Marco
authors: M
authors: Gattorno
authors: Anna
authors: A
authors: Rubartelli
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis* / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D046529:Microscopy, Electron, Transmission; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6