Time-course of neopterin levels in patients suffering from severe sepsis treated with and without Drotrecogin-alpha (activated)

Neopterin is secreted by activated monocytes/macrophages upon stimulation with interferon-gamma. The release of this pro-inflammatory mediator permits the activation status of cell-mediated immune system to be examined. We assayed neopterin plasma concentrations in septic patients under treatment with (n = 10) and without Drotrecogin-alpha (activated) (n = 10) on d 1 and 6 of severe sepsis. In septic patients treated with Drotrecogin-alpha (activated), neopterin levels decreased significantly (p = 0.027) from d 1 (baseline) (mean 140.8 nmol/l, +/- standard error of mean (SEM) 106.2) to d 6 (mean 68.9 nmol/l, +/- SEM 46.4). In patients not treated with Drotrecogin-alpha (activated) there was no significant (p = 0.96) decrease of neopterin levels from d 1 mean 147.8 nmol/l, +/- SEM 58.4) to d 6 (mean 139.7 nmol/l, +/- SEM 52.6). Furthermore, neopterin levels showed significant correlations with bilirubin in all patient groups on d 1 of severe sepsis (range of correlation coefficient, r : 0.69-0.88; p < 0.05). Neopterin levels correlated significantly with creatinine with regard to all patient groups (range of correlation coefficient, r: 0.73-0.92; p < 0.05). In conclusion, Drotrecogin-alpha (activated) was associated with a significant decrease of neopterin plasma levels in septic patients. Neopterin concentrations appear to depend on renal function and enterohepatic circulation.