title: Cysteine redox potential determines pro-inflammatory IL-1beta levels.
abstract: BACKGROUND
  Cysteine (Cys) and its disulfide, cystine (CySS) represent the major extracellular thiol/disulfide redox control system. The redox potential (E(h)) of Cys/CySS is centered at approximately -80 mV in the plasma of healthy adults, and oxidation of E(h) Cys/CySS is implicated in inflammation associated with various diseases.
  
  
  RESULTS
  The purpose of the present study was to determine whether oxidized E(h) Cys/CySS is a determinant of interleukin (IL)-1beta levels. Results showed a 1.7-fold increase in secreted pro-IL-1beta levels in U937 monocytes exposed to oxidized E(h) Cys/CySS (-46 mV), compared to controls exposed to a physiological E(h) of -80 mV (P<0.01). In LPS-challenged mice, preservation of plasma E(h) Cys/CySS from oxidation by dietary sulfur amino acid (SAA) supplementation, was associated with a 1.6-fold decrease in plasma IL-1beta compared to control mice fed an isonitrogenous SAA-adequate diet (P<0.01). Analysis of E(h) Cys/CySS and IL-1beta in human plasma revealed a significant positive association between oxidized E(h) Cys/CySS and IL-1beta after controlling for age, gender, and BMI (P<0.001).
  
  
  CONCLUSIONS
  These data show that oxidized extracellular E(h) Cys/CySS is a determinant of IL-1beta levels, and suggest that strategies to preserve E(h) Cys/CySS may represent a means to control IL-1beta in inflammatory disease states.
authors.affiliation: Nutrition and Health Sciences Program, Emory University, Atlanta, GA, USA.
authors.forename: Smita S
authors.initials: SS
authors.lastname: Iyer
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Accardi
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ziegler
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Blanco
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Ritzenthaler
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rojas
authors.forename: Jesse
authors.initials: J
authors.lastname: Roman
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones