Cysteine redox potential determines pro-inflammatory IL-1beta levels

PLoS One. 2009;4(3):e5017. doi: 10.1371/journal.pone.0005017. Epub 2009 Mar 27.


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.

Methodology/principal findings: 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/significance: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cysteine / metabolism*
  • Diet
  • Humans
  • Inflammation / metabolism*
  • Interleukin-1beta / analysis*
  • Mice
  • Monocytes / cytology
  • Monocytes / metabolism
  • Oxidation-Reduction
  • U937 Cells


  • Interleukin-1beta
  • Cysteine