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

Abstract

Background: Cysteine (Cys) and its disulfide, cystine (CySS) represent the major extracellular thiol/disulfide redox control system. The redox potential (Eh) of Cys/CySS is centered at approximately - 80 mV in the plasma of healthy adults, and oxidation of Eh Cys/ CySS is implicated in inflammation associated with various diseases. Methodology/Principal Findings: The purpose of the present study was to determine whether oxidized Eh Cys/CySS is a determinant of interleukin (IL)-1β levels. Results showed a 1.7-fold increase in secreted pro-IL-1b levels in U937 monocytes exposed to oxidized Eh Cys/CySS (- 46 mV), compared to controls exposed to a physiological Eh of - 80 mV (P,0.01). In LPS-challenged mice, preservation of plasma Eh Cys/CySS from oxidation by dietary sulfur amino acid (SAA) supplementation, was associated with a 1.6-fold decrease in plasma IL-1β compared to control mice fed an isonitrogenous SAA-adequate diet (P,0.01). Analysis of Eh Cys/ CySS and IL-1β in human plasma revealed a significant positive association between oxidized Eh Cys/CySS and IL-1β after controlling for age, gender, and BMI (P<0.001). Conclusions/Significance: These data show that oxidized extracellular Eh Cys/CySS is a determinant of IL-1β levels, and suggest that strategies to preserve Eh Cys/CySS may represent a means to control IL-1β in inflammatory disease states. © 2009 Iyer et al.