Tryptophan degradation by the
enzyme indoleamine-(2,3)-dioxy genase (IDO) and
neopterin production are induced within cellular immune activation by stimulation of monocyte-derived macrophages and dendritic cells with
cytokine interferon-gamma. Deprivation of
tryptophan represents an important antimicrobial and antitumoral immune defence mechanism but it also suppresses T-cell proliferation. Recently
tryptophan degradation by
tumor cells was proposed as strategy to escape immune response. In this study the relationship between
tryptophan degradation and immune activation was examined in 20 patients with gynecological
cancer. Concentrations of
tryptophan and
kynurenine were measured by HPLC in sera of patients, and to estimate IDO activity, the
kynurenine to
tryptophan ratio was calculated. In parallel,
neopterin concentrations were measured by ELISA.
Tryptophan concentrations (median, interquartile range: 43.5, 31.2-56.3 microM) were lower in patients with gynecological
cancer compared to healthy individuals of similar age (53.5, 47.0-64.2 microM; P<0.05).
Kynurenine concentrations (median: 1.91 vs. 1.73 microM in controls) and kyn/trp (median: 41 vs. 35 micromol/mmol in controls) were slightly higher in patients, but not significantly different.
Neopterin concentrations were significantly higher in patients (median: 10.8 vs. 7.0 nM in controls; P<0.05) and correlated with the
kynurenine per
tryptophan ratio (r(s)=0.555; P<0.02). In conclusion,
tryptophan degradation is detectable in patients with gynecological
cancer. The relationship between kyn/trp and
neopterin concentrations indicates that cellular immune activation rather than
tumor-mediated IDO-activity is responsible (228 words).