The concentration of Trx1 in human plasma is in the low nanomolar range (1-5 nM), and is found to be elevated several-fold under inflammatory conditions (Yoshida et al, 1999) . However, plasma Trx1 is oxidized and appears to represent systemic dilution of Trx1 previously released within tissues. Accordingly, local tissue concentrations of secretory Trx1, for example, within activated lymph nodes, are expected to be markedly higher than in plasma. Overall Trx1 concentrations in mammalian tissues can be as high as 20 mM (Gromer et al, 2004) . Certain Trx1-secreting cell types, including macrophages and dendritic cells, distinctly upregulate expression of Trx1 upon activation (Angelini et al, 2002) . In vitro studies of Trx1 secretion suggest that a substantial fraction of intracellular Trx1 can be released within a few hours (Rubartelli et al, 1992) . Although direct measurements of extracellular Trx1 within tissues are not available, physiologically relevant extracellular Trx1 concentrations may well reach into the upper nanomolar, if not lower micromolar range.