S51 Thioredoxin modifies MIF release from human monocytes following stimulation with LTA and LPS. (16th November 2010)

• Record Type: Journal Article
• Authors: Leaver, S K; Quinlan, G J; Evans, T W; Burke-Gaffney, A
• Is Part Of: Thorax. Volume 65(2010)Supplement 4
• Page Start: A25
• Page End: A26
• Publication Date: 2010-11-16
• Subjects: Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thx.2010.150938.2
• Languages: English
• ISSNs: 0040-6376

Abstract

Abstract : Rationale: Thioredoxin (Trx) is a 12-kDa ubiquitous redox-active thiol (-SH) protein. Plasma levels of Trx are raised in numerous medical and surgical conditions associated with oxidative stress and inflammation such as sepsis (Burke-Gaffney 2005). Trx is thought to have an anti-inflammatory role, at least when released into the circulation. By contrast macrophage migration inhibitory factor (MIF) is regarded as a pivotal pro-inflammatory protein. Indeed co-injection of MIF and E. coli enhanced lethality, whereas, anti-MIF monoclonal antibodies conferred protection against murine caecal ligation and puncture and administration of E. coli (Calandra 2000). We have previously reported a positive correlation between Trx and MIF in adults with SIRS/sepsis. (Leaver 2009) Furthermore Trx was shown to inhibit the secretion of MIF in THP-1 cells (Tamaki 2006). The aim of this study was to determine the effect of exogenous Trx on the release of MIF and for comparison IL-8 and IL-10 from primary human monocytes at baseline and following stimulation with lipoteichoic acid (LTA) or lipopolysaccharide (LPS). Methods: Monocytes were extracted from whole blood of healthy volunteers using Percoll gradients and MACS columns. Monocytes (1×10 6 cells/ml) were pre-incubated with Trx (0.1–10 000 nM) for 24 h followed by treatment (24 h) with medium alone, LPS 1 μg/ml, LTA 10μg/ml. MIF, IL-8 and IL-10 concentrations in cell supernatants were determined by ELISA. Results: Following incubation with Trx there was no significant change in MIF release from monocytes. By contrast, LPS and LTA significantly (p<0.01) induced MIF from base line. When monocytes were treated with LPS (Abstract S51 Figure 1 ) or LTA following pre-incubation with Trx, MIF release was significantly less than the theoretical additive effects of the two treatments alone. By contrast, although Trx significantly induced IL-8 and IL-10, Trx did not modulate LPS or LTA induced cytokine release. Conclusion: Trx reduced MIF release following stimulation with LPS and LTA. Extracellular Trx exerts an anti-inflammatory effect in this model. The Trx/MIF axis should be explored as a potential route for therapeutic intervention in patients with sepsis.