title: Monocytes from familial cold autoinflammatory syndrome patients are activated by mild hypothermia.
abstract: BACKGROUND
  Familial cold autoinflammatory syndrome (FCAS) is characterized by rash, fever, and arthralgia in response to cold exposure. CIAS1, the gene that codes for cryopyrin, is mutated in FCAS. Treatment with anakinra (IL-1 receptor antagonist) prevents symptoms, indicating a crucial role for IL-1 in this disease.
  
  
  OBJECTIVE
  To study cytokine responses to cold exposure in monocytes from subjects with FCAS.
  
  
  METHODS
  Adherence-enriched monocytes were incubated at 32 degrees C or 37 degrees C. Transcription and release of IL-1beta, IL-6, and TNF-alpha were monitored by quantitative PCR and ELISA.
  
  
  RESULTS
  The FCAS monocytes but not control cells responded to 4 h incubation at 32 degrees C with significant secretion of IL-1beta. At 16 h, IL-1beta, IL-6, and TNF-alpha were all significantly elevated in FCAS monocytes at 32 degrees C. Increased cytokine transcription was observed in all monocytes at 4 hours, but at 16 hours it was only seen in FCAS monocytes incubated at 32 degrees C. Incubation at 32 degrees C for as little as 1 hour sufficed to induce measurable IL-1beta release. Caspase-1 inhibitors prevented the cold-induced IL-1beta release, whereas a purinergic antagonist did not. Anakinra had no effect on the early IL-1beta release but significantly reduced the late-phase transcription and release of all cytokines.
  
  
  CONCLUSIONS
  FCAS monocytes respond to mild hypothermia with IL-1beta release, which in turn induces autocrine transcription and secretion of IL-6 and TNF-alpha as well as stimulation of further IL-1beta production.
  
  
  CONCLUSIONS
  These results confirm the central role of IL-1beta in FCAS and support the use of IL-1 targeted therapy in these patients.
authors.affiliation: Division of Rheumatology, Allergy and Immunology, University of California at San Diego School of Medicine, La Jolla, CA 92093-0635, USA.
authors.forename: Sanna
authors.initials: S
authors.lastname: Rosengren
authors.forename: James L
authors.initials: JL
authors.lastname: Mueller
authors.forename: Justin P
authors.initials: JP
authors.lastname: Anderson
authors.forename: Brian L
authors.initials: BL
authors.lastname: Niehaus
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Misaghi
authors.forename: Scott
authors.initials: S
authors.lastname: Anderson
authors.forename: David L
authors.initials: DL
authors.lastname: Boyle
authors.forename: Hal M
authors.initials: HM
authors.lastname: Hoffman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D003080:Cold Temperature; D005260:Female; D006801:Humans; D007035:Hypothermia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human