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Increased plasma thioredoxin levels in patients with sepsis: positive association with macrophage migration
Susannah K Leaver1, Niall S MacCallum, Vasisht Pingle
1Unit of Critical Care, Respiratory Science, National Heart and Lung Institute Division, Faculty of Medicine, Imperial College London, London SW3-6LY, UK.
Purpose:
To establish the relationship between plasma levels of thioredoxin (Trx) and macrophage migration inhibitory factor (MIF) in systemic inflammatory stress syndrome (SIRS)/sepsis.
Methods:
Enzyme-linked immunosorbent assay measurements of Trx, MIF, IL-6, -8, and -10 and enzyme-linked fluorescent assay determination of procalcitonin (PCT) in plasma from patients with SIRS/sepsis, neutropenic sepsis, healthy volunteers and pre-oesophagectomy patients.
Results:
Thioredoxin was significantly higher in SIRS/sepsis patients [101.3 ng ml(-1), interquartile range (IQR) 68.7-155.6, n = 32] compared with that in healthy controls (49.5 ng ml(-1), IQR 31.4-71.1, P < 0.001, n = 17) or pre-oesophagectomy patients (40.5 ng ml(-1), IQR 36.9-63.2, P < 0.01, n = 7), but was not raised in neutropenics (n = 5). MIF levels were also significantly higher in SIRS/sepsis patients (12.1 ng ml(-1), IQR 9.5-15.5, n = 35), but not in the neutropenic group, when compared with healthy controls (9.3 ng ml(-1), IQR 7.3-10.7, P < 0.01, n = 20). Trx levels correlated, positively, with MIF levels and APACHE II scores. Plasma levels of IL-6, -8 and -10 and PCT increased significantly in patients with SIRS/sepsis (P < 0.001) and with neutropenic sepsis, but did not correlate with Trx or MIF levels.
Conclusion:
Plasma levels of Trx, MIF, IL-6, -8, -10 and PCT were raised in patients with SIRS/sepsis. Comparisons between mediators suggest a unique correlation of Trx with MIF. Moreover, Trx and MIF differed from cytokines and PCT in that levels were significantly lower in patients with neutropenia compared with the main SIRS/sepsis group. By contrast, IL-8 and PCT levels were significantly greater in the neutropenic patient group. The link between MIF and Trx highlighted in this study has implications for future investigations into the pathogenesis of SIRS/sepsis.