Figure 5.

Inflammation markers

(A) Tryptophan can be metabolized along several distinct pathways either giving rise to the neurotransmitter serotonin, along the kynurenine pathway that has been associated with inflammation and disease, or to several indole compounds. Kynurenine in liver is generated by tryptophan dioxygenase (TDO) but in extra-hepatic tissues by the enzyme indoleamine 2,3-dioxygenase (IDO), which is well characterized to be induced by the inflammatory cytokines, interferon-gamma (IFNγ), and tumor necrosis factor alpha (TNF-α). Kynurenine can further be metabolized to quinolinate that is a precursor of nicotinamide adenine dinucleotide (NAD⁺). Metabolites that were detected in samples are marked with rectangular broken lines around them; red indicates higher levels and green represents lower levels in EC relative to VP. IDO, Indoleamine 2,3-dioxygenase; IFN γ, Interferon gamma; NAD⁺, nicotinamide adenine dinucleotide; TDO, tryptophan 2,3-dioxygenase; TNF-α, tumor necrosis factor alpha.

(B) Boxplots of metabolites that belong to kynurenine pathway. Log2 of serotonin, tryptophan, kynurenine, and quinolinate are presented for EC (orange), HC (green), and VP (red). Median values and interquartile ranges are indicated by bars. p values are determined by Mann-Whitney U test. ∗p value<0.05, ∗∗p value<0.01, and ∗∗∗p value<0.001.

(C) Partial least squares-discriminant analysis (PLS-DA) including 41 proteins analyzed in plasma samples showing clustering of the three study groups EC (orange), HC (green), and VP (red) samples where VP samples cluster separately from HC and EC, whereas HC and EC intermingle to a small extend.

(D) Boxplots of proteins that had significantly different levels in HC and EC (p < 0.05) revealed by Mann-Whitney U test. Log2 of CCL4, CCL7, CCL20, and NOS3 are presented for EC (orange), HC (green), and VP (red). Median values and interquartile ranges are indicated by bars. ∗p value<0.05, ∗∗p value<0.01, ∗∗∗p value<0.001. Data shown include samples of HC (n = 12), EC (n = 14), and VP (n = 16).

See also Figure S6 for plasma levels of CRP and Neopterin.