title: Inflammasome mRNA expression in human monocytes during early septic shock.
abstract: BACKGROUND
  Monocytes are central to the initiation of the inflammatory response in sepsis, with caspase-1 activation playing a key role. Monocyte deactivation during sepsis has been linked to poor outcomes.
  
  
  OBJECTIVE
  Given the importance of caspase-1 in the immune response, we investigated whether monocytes from patients early in septic shock demonstrate alterations in mRNAs for caspase-1-related molecules.
  
  
  METHODS
  Patients with septic shock (n = 26; age >18 years), critically ill intensive care unit patients (n = 20), and healthy volunteers (n = 22) were enrolled in a prospective cohort study in a university intensive care unit. Demographic, biological, physiologic, and plasma cytokine measurements were obtained. Monocytes were assayed for ex vivo tumor necrosis factor-alpha production, and fresh monocyte mRNA was analyzed by quantitative reverse-transcription polymerase chain reaction for Toll-like receptors, NOD-LRR proteins, cytokines, and nuclear factor-kappaB-related genes.
  
  
  RESULTS
  Relative copy numbers for the inflammasome mRNAs for ASC, caspase-1, NALP1, and Pypaf-7 were significantly lower in patients with septic shock compared with critically ill control subjects. NALP1 mRNA levels were linked to survival in patients with sepsis (P = 0.0068) and correlated with SAPS II scores (r = -0.63).
  
  
  CONCLUSIONS
  These data suggest that monocyte deactivation occurs during the earliest stages of the systemic inflammatory response and that changes in inflammasome mRNA expression are part of this process.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University Medical Center, Columbus, Ohio, USA.
authors.forename: Ruairi J
authors.initials: RJ
authors.lastname: Fahy
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Exline
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Gavrilin
authors.forename: Nitin Y
authors.initials: NY
authors.lastname: Bhatt
authors.forename: Beth Y
authors.initials: BY
authors.lastname: Besecker
authors.forename: Anasuya
authors.initials: A
authors.lastname: Sarkar
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hollyfield
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Duncan
authors.forename: Haikady N
authors.initials: HN
authors.lastname: Nagaraja
authors.forename: Nina L
authors.initials: NL
authors.lastname: Knatz
authors.forename: Mark
authors.initials: M
authors.lastname: Hall
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wewers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D053468:CARD Signaling Adaptor Proteins; D020170:Caspase 1 / Q000096:biosynthesis / Q000235:genetics*; D016638:Critical Illness; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology; D000070576:NLR Proteins; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human; C476731:NLRP12 protein, human; C402202:PYCARD protein, human; D012333:RNA, Messenger; D020170:Caspase 1