Enhanced tryptophan degradation in systemic lupus erythematosus

In vitro and in vivo, tryptophan degradation was found to be associated wit h T cell functional loss and tolerance induction. In systemic lupus erythem atosus (SLE) besides the Th2-type cytokine interleukin-10, Th1-type cytokin es including interferon-gamma (IFN-gamma) are expressed especially during e xacerbation of the disease. IFN-gamma stimulates the enzyme indoleamine (2, 3)dioxygenase (IDO) converting tryptophan to the metabolite kynurenine whic h in macrophages is subsequently degraded to other, partly neurotoxic compo unds like quinolinic acid, and finally to nicrotinamides. We measured kynur enine and tryptophan concentrations in the sera of 55 SLE patients. In thes e patients, the concentrations of tryptophan (median, interquartile range: 53.9, 45.7-64.1 mu M) were lower (p < 0.0001), and the kynurenine concentra tions (2.45, 1.75-3.40 mu M) were increased (p < 0.0005) compared to health y blood donors (70.0, 63.8-80.6; 1.80, 1.45-2.27 mu M, respectively). Also the kynurenine per tryptophan quotients (K/T), which allow to estimate IDO activity, were significantly higher in patients than in normals (0.043, 0.0 33-0.062 vs. 0.027, 0.021-0.030; p < 0.0001), indicating enhanced IDO-induc ed tryptoyhan degradation in SLE. There was no significant relationship bet ween tryp- tophan, kynurenine and the SLEDAI, and also the correlation of K /T with SLEDAI was rather weak (r(s) = 0.243, p < 0.05). Higher K/T was fou nd in patients presenting with serositis (p = 0.01), decrease of complement (c3, c4; p < 0.01) and blood count change (anemia, leucopenia, lymphopenia ; p = 0.032) than in patients without such disease manifestations. The sign ificant correlation found between K/T and neopterin (r(s) = 0.808, p < 0.00 1), a marker of immune activation paints to a role of immune activation to be responsible for tryptophan degradation in SLE patients.