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

Abstract

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.

Alterations of leptin in the course of inflammation and severe sepsis

“…Several in-vitro studies already demonstrated specific anti-inflammatory effects of DAA, e.g. inhibition of transcription factor NF-kappa B in isolated mononuclear cells or the inhibition of macrophage inflammatory protein-1 (MIP-1-alpha), monocyte chemoattractant protein-1 (MCP-1), neopterin [19], [43], [44] or up-regulation of adiponectin [45]. However, the role of specifically leptin during severe sepsis is not yet completely understood.…”