In vitro Measured Indoleamine 2, 3-dioxygenase Activity Correlates with Inflammation and Tryptophan Levels In vivo

Abstract

Aims: To evaluate the diagnostic validity of an in vitro assay for indoleamine 2,3-dioxygenase (IDO) activity as indicator for biological alterations that are associated with depressive symptomatologies. Study Design: Retrospective evaluation of a medical database. Place and Duration of Study: Institute for Medical Diagnostics, Berlin, between April and July 2013. Methodology: We compared values for IDOin vitro, a so far unpublished assay for IDO activity that measures tryptophan degradation in peripheral blood monocytic cell (PBMC), with blood levels of tryptophan and tumor necrosis factor alpha (TNF-alpha). Values were derived from a clinical database comprising 441 patients who had received IDOin vitro, tryptophan and/or TNF-alpha testing in the course of medical treatment between May 2011 and March 2013. All data was anonymized. Clinical significance of IDOin vitro was evaluated by correlation of IDOin vitro to blood tryptophan and TNF-alpha α levels. Further, we challenged the validity of the IDOin vitro assay by investigating the influence of the PBMC proliferation rate as a potential confounding factor and comparing the responses to phythemagglutinin (PHA) and interferon-gamma (IFN-gamma), a recognized inducer of IDO activity. Results: Low plasma tryptophan and high serum TNF-alpha are associated with increased IDOin vitro (2.8±3.3 vs. 2.2±1.1, P=0.04 and 2.7±3.5 vs. 2.1±1.6, P=0.05). Elevated IDOin vitro is not due to increased PBMC proliferation rates. PHA and IFN-gamma yield correlating IDOin vitro  values (correlation coefficient=0.91). Conclusions: IDOin vitro represents a valid diagnostic tool for IDO activity and correlates with inflammation and decreased availability of tryptophan in vivo. IDOin vitro may therefore serve as a biomarker to examine the interaction of inflammation and tryptophan metabolism that underlies a subgroup of depressive symptomatologies.