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Deficient production of IL-1 receptor antagonist and IL-6 coupled to oxidative stress in cryopyrin-associated periodic syndrome monocytes
  1. Sonia Carta1,
  2. Sara Tassi1,
  3. Laura Delfino1,
  4. Alessia Omenetti2,3,
  5. Salvatore Raffa4,5,
  6. Maria Rosaria Torrisi4,5,
  7. Alberto Martini2,3,
  8. Marco Gattorno2,3,
  9. Anna Rubartelli1
  1. 1Cell Biology Unit, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
  2. 22nd Division of Pediatrics, ‘G. Gaslini’ Institute, Genova, Italy
  3. 3Department of Pediatrics, University of Genoa, Genova, Italy
  4. 4Dipartimento di Medicina Clinica e Molecolare, Istituto Pasteur-Fondazione Cenci Bolognetti University of Rome Sapienza, Rome, Italy
  5. 5Laboratory of Cellular Diagnostics, Azienda Ospedaliera S. Andrea, Rome, Italy
  1. Correspondence to Anna Rubartelli, Cell Biology Unit, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, Genova 16132, Italy; anna.rubartelli{at}


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.

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  • Funding Telethon Italia (GGP09127), Compagnia San Paolo, MIUR, Associazione Italiana per la Ricerca sul Cancro (IG 10272). SC is the recipient of the ‘Young Investigators’ grant GR-2010-2309622 from the Italian Ministry of Health.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was obtained from the ethical board of the G. Gaslini Institute.

  • Provenance and peer review Not commissioned; externally peer reviewed.