Prognostic value of platelet-derived growth factor in patients with severe sepsis

Primary objective: Platelet-derived growth factor-BB (PDGF-BB) has been shown to promote the structural integrity of the vessel wall and to increase wound healing capacity. Aim of the present study was to determine the role of PDGF-BB in the context of outcome of septic patients. Furthermore, the effect of treatment with recombinant human activated protein C (rhAPC) on plasma levels of PDGF-BB in severe sepsis was evaluated as well as the in vitro effect of rhAPC on PDGF-BB-release from human endothelial cells (HUVEC). Research design, methods and procedures: PDGF-BB levels were measured in 46 patients on day 3 of severe sepsis. Twenty-one of these patients received treatment with rhAPC. The in vitro effect of rhAPC on PDGF-BB-messenger RNA synthesis and release of PDGF-BB into supernatants was measured by reverse transcriptase-polymerase chain reaction and ELISA-methods. Main outcomes and results: Survivors of severe sepsis presented with higher PDGF-BB levels than non-survivors (p < 0.05). Septic patients with PDGF-BB levels below 200 pg/ml were 7.3 times more likely (RR 7.3, 95% CI: 1.4-44.5; p < 0.05) to die from sepsis than patients with higher PDGF-BB values. RhAPC (1-10 mu g/ml) stimulated endothelial PDGF-BB-messenger RNA transcription and PDGF-BB-release in vitro. Plasma levels of PDGF-BB in patients receiving rhAPC were significantly (p < 0.01) higher (median 277.7; 25-75th percentiles: 150.5-414.4 pg/ml) than in patients not treated with rhAPC ( median: 125.6; 25-75th percentiles: 55.3-344.7 pg/ml). Conclusions: The ability of rhAPC to upregulate endothelial PDGF-BB production may represent a new molecular mechanism by which rhAPC controls vessel wall homeostasis and increases tissue healing capacity in severe sepsis. PDGF-BB may serve as useful laboratory marker to predict survival in patients presenting with severe sepsis.